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Huang Y, Yao K, Zhang Q, Huang X, Chen Z, Zhou Y, Yu X. Bioelectronics for electrical stimulation: materials, devices and biomedical applications. Chem Soc Rev 2024; 53:8632-8712. [PMID: 39132912 DOI: 10.1039/d4cs00413b] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/13/2024]
Abstract
Bioelectronics is a hot research topic, yet an important tool, as it facilitates the creation of advanced medical devices that interact with biological systems to effectively diagnose, monitor and treat a broad spectrum of health conditions. Electrical stimulation (ES) is a pivotal technique in bioelectronics, offering a precise, non-pharmacological means to modulate and control biological processes across molecular, cellular, tissue, and organ levels. This method holds the potential to restore or enhance physiological functions compromised by diseases or injuries by integrating sophisticated electrical signals, device interfaces, and designs tailored to specific biological mechanisms. This review explains the mechanisms by which ES influences cellular behaviors, introduces the essential stimulation principles, discusses the performance requirements for optimal ES systems, and highlights the representative applications. From this review, we can realize the potential of ES based bioelectronics in therapy, regenerative medicine and rehabilitation engineering technologies, ranging from tissue engineering to neurological technologies, and the modulation of cardiovascular and cognitive functions. This review underscores the versatility of ES in various biomedical contexts and emphasizes the need to adapt to complex biological and clinical landscapes it addresses.
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Affiliation(s)
- Ya Huang
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Kuanming Yao
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Qiang Zhang
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Xingcan Huang
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Zhenlin Chen
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Yu Zhou
- Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Hong Kong, China.
| | - Xinge Yu
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
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Ozyigit F, Deger AN, Kocak FE, Ekici MF, Simsek H, Arık O. Protective effects of hesperidin in gastric damage caused by experimental ischemia-reperfusion injury model in rats. Acta Cir Bras 2024; 39:e391124. [PMID: 38477785 DOI: 10.1590/acb391124] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 12/11/2023] [Indexed: 03/14/2024] Open
Abstract
PURPOSE This study evaluated the protective effect of hesperidin on injury induced by gastric ischemia-reperfusion. METHODS Fifty male Sprague Dawley rats (250-300 g) were divided into five groups: control (C), sham (S), ischemia (I), ischemia-reperfusion (I/R) and hesperidin + ischemia-reperfusion (Hes + I/R). Hesperidin was injected intraperitoneally at the dose of 100 mg/kg one hour before the experimental stomach ischemia-reperfusion. Celiac artery was ligated. After 45 minutes ischemia and 60 minutes reperfusion period, blood samples were obtained under anesthesia. Then, animals were sacrificed, stomach tissues were excised for biochemical, and histopathological analyses were performed. Malondialdehyde levels and superoxide dismutase, glutathione peroxidase activities and total antioxidant status (TAS), total oxidant status (TOS), protein, total thiol parameters were measured in plasma, and tissue homogenate samples. H + E, periodic acid-Schiff, hypoxia inducible factor, terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end-labeling (TUNEL), and proliferating cell nuclear antigen (PCNA) for cell proliferation as immunohistochemical parameters were determined. RESULTS Upon biochemical and histopathological assessment, hesperidin decreased stomach tissue changes in comparison with IR group. Ischemia-reperfusion injury led to a considerably increase in malondialdehyde, protein, and TOS levels (p < 0.001) in stomach tissue. Hesperidin treatment significantly decreased malondialdehyde, protein, and TOS levels (p < 0.001). Hesperidin increased superoxide dismutase, TAS, total thiol and glutathione peroxidase activities in comparison with IR group. Hesperidin reduced damage and also increased TUNEL and PCNA immunoreactivity in stomach tissue. CONCLUSIONS Hesperidin was able to decrease I/R injury of the stomach tissue due to inhibition of lipid peroxidation and protein oxidation, duration of antioxidant, and free radical scavenger properties. Consequently, hesperidin can provide a beneficial therapeutic choice for preventing stomach tissue ischemia-reperfusion injury in clinical application.
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Affiliation(s)
- Filiz Ozyigit
- Bandirma Onyedi Eylul University - Faculty of Medicine - Department of Pharmacology - Bandirma, Turkey
| | - Ayse Nur Deger
- Kutahya Health Sciences University - Faculty of Medicine - Department of Pathology - Kutahya, Turkey
| | - Fatma Emel Kocak
- Kutahya Health Sciences University - Faculty of Medicine - Department of Medical Biochemistry - Kutahya, Turkey
| | - Mehmet Fatih Ekici
- Kutahya Health Sciences University - Faculty of Medicine - Department of General Surgery - Kutahya, Turkey
| | - Hasan Simsek
- Aksaray University - Faculty of Medicine - Department of Physiology - Aksaray, Turkey
| | - Ozlem Arık
- Kutahya Health Sciences University - Faculty of Medicine - Department of Biostatistics - Kutahya, Turkey
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Basturkmen B, Ergene E, Doganay D, Yilgor Huri P, Unalan HE, Aksoy EA. Silver nanowire loaded poly(ε-caprolactone) nanocomposite fibers as electroactive scaffolds for skeletal muscle regeneration. BIOMATERIALS ADVANCES 2022; 134:112567. [PMID: 35527139 DOI: 10.1016/j.msec.2021.112567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 11/19/2021] [Accepted: 11/23/2021] [Indexed: 06/14/2023]
Abstract
Volumetric muscle loss (VML) due to trauma and tumor removal operations affects millions of people every year. Although skeletal muscle has a natural repair mechanism, it cannot provide self-healing above a critical level of VML. In this study, nanocomposite aligned fiber scaffolds as support materials were developed for volumetric skeletal muscle regeneration. For this purpose, silver nanowire (Ag NW) loaded poly(ε-caprolactone) (PCL) nanocomposite fiber scaffolds (PCL-Ag NW) were prepared to mimic the aligned electroactive structure of skeletal muscle and provide topographic and conductive environment to modulate cellular behavior and orientation. A computer-aided rotational wet spinning (RWS) system was designed to produce high-yield fiber scaffolds. Nanocomposite fiber bundles with lengths of 50 cm were fabricated via this computer-aided RWS system. The morphological, chemical, thermal properties and biodegradation profiles of PCL and PCL-Ag NW nanocomposite fibers were characterized in detail. The proliferation behavior and morphology of C2C12 mouse myoblasts were investigated on PCL and PCL-Ag NW nanocomposite fibrous scaffolds with and without electrical stimulation. Significantly enhanced cell proliferation was observed on PCL-Ag NW nanocomposite fibers compared to neat PCL fibers with electrical stimulations of 1.5 V, 3 V and without electrical stimulation.
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Affiliation(s)
- Berk Basturkmen
- Department of Polymer Science and Technology, Hacettepe University, Ankara 06800, Turkey
| | - Emre Ergene
- Department of Biomedical Engineering, Ankara University, Ankara 06830, Turkey
| | - Doga Doganay
- Department of Metallurgical and Materials Engineering, Middle East Technical University (METU), Ankara 06800, Turkey
| | - Pinar Yilgor Huri
- Department of Biomedical Engineering, Ankara University, Ankara 06830, Turkey
| | - Husnu Emrah Unalan
- Department of Metallurgical and Materials Engineering, Middle East Technical University (METU), Ankara 06800, Turkey
| | - Eda Ayse Aksoy
- Department of Polymer Science and Technology, Hacettepe University, Ankara 06800, Turkey; Department of Basic Pharmaceutical Sciences, Hacettepe University, Ankara 06100, Turkey.
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Guo R, Liao M, Ma X, Hu Y, Qian X, Xiao M, Gao X, Chai R, Tang M. Cochlear implant-based electric-acoustic stimulation modulates neural stem cell-derived neural regeneration. J Mater Chem B 2021; 9:7793-7804. [PMID: 34586130 DOI: 10.1039/d1tb01029h] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Cochlear implantation is considered to be the best therapeutic method for profound sensorineural hearing loss, but insufficient numbers of functional spiral ganglion neurons hinder the clinical effects of cochlear implantation. Stem cell transplantation has the potential to provide novel strategies for spiral ganglion neuron regeneration after injury. However, some obstacles still need to be overcome, such as low survival and uncontrolled differentiation. Several novel technologies show promise for modulating neural stem cell behaviors to address these issues. Here, a device capable of electrical stimulation was designed by combining a cochlear implant with a graphene substrate. Neural stem cells (NSCs) were cultured on the graphene substrate and subjected to electrical stimulation transduced from sound waves detected by the cochlear implant. Cell behaviors were studied, and this device showed good biocompatibility for NSCs. More importantly, electric-acoustic stimulation with higher frequencies and amplitudes induced NSC death and apoptosis, and electric-acoustic stimulation could promote NSCs to proliferate and differentiate into neurons only when low-frequency stimulation was supplied. The present study provides experimental evidence for understanding the regulatory role of electric-acoustic stimulation on NSCs and highlights the potentials of the above-mentioned device in stem cell therapy for hearing loss treatment.
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Affiliation(s)
- Rongrong Guo
- Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College, Soochow University, Suzhou, 215000, China. .,State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.,Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, School of Life Science and Technology, Southeast University, Nanjing 210096, China.
| | - Menghui Liao
- Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, School of Life Science and Technology, Southeast University, Nanjing 210096, China. .,Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
| | - Xiaofeng Ma
- Department of Otorhinolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210008, China.,Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing, Jiangsu 210008, China. .,Research Institution of Otorhinolaryngology, Nanjing, Jiangsu 210008, P. R. China
| | - Yangnan Hu
- Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, School of Life Science and Technology, Southeast University, Nanjing 210096, China. .,Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
| | - Xiaoyun Qian
- Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing, Jiangsu 210008, China. .,Research Institution of Otorhinolaryngology, Nanjing, Jiangsu 210008, P. R. China
| | - Miao Xiao
- Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College, Soochow University, Suzhou, 215000, China.
| | - Xia Gao
- Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing, Jiangsu 210008, China. .,Research Institution of Otorhinolaryngology, Nanjing, Jiangsu 210008, P. R. China
| | - Renjie Chai
- Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, School of Life Science and Technology, Southeast University, Nanjing 210096, China. .,Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
| | - Mingliang Tang
- Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College, Soochow University, Suzhou, 215000, China. .,Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, School of Life Science and Technology, Southeast University, Nanjing 210096, China. .,Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
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The Roles of GABA in Ischemia-Reperfusion Injury in the Central Nervous System and Peripheral Organs. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:4028394. [PMID: 31814874 PMCID: PMC6878816 DOI: 10.1155/2019/4028394] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 09/27/2019] [Accepted: 10/18/2019] [Indexed: 12/30/2022]
Abstract
Ischemia-reperfusion (I/R) injury is a common pathological process, which may lead to dysfunctions and failures of multiple organs. A flawless medical way of endogenous therapeutic target can illuminate accurate clinical applications. γ-Aminobutyric acid (GABA) has been known as a marker in I/R injury of the central nervous system (mainly in the brain) for a long time, and it may play a vital role in the occurrence of I/R injury. It has been observed that throughout cerebral I/R, levels, syntheses, releases, metabolisms, receptors, and transmissions of GABA undergo complex pathological variations. Scientists have investigated the GABAergic enhancers for attenuating cerebral I/R injury; however, discussions on existing problems and mechanisms of available drugs were seldom carried out so far. Therefore, this review would summarize the process of pathological variations in the GABA system under cerebral I/R injury and will cover corresponding probable issues and mechanisms in using GABA-related drugs to illuminate the concern about clinical illness for accurately preventing cerebral I/R injury. In addition, the study will summarize the increasing GABA signals that can prevent I/R injuries occurring in peripheral organs, and the roles of GABA were also discussed correspondingly.
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Gao L, Zhao H, Zhu T, Liu Y, Hu L, Liu Z, Huang H, Chen F, Deng Z, Chu D, Du D. The Regulatory Effects of Lateral Hypothalamus Area GABA B Receptor on Gastric Ischemia-Reperfusion Injury in Rats. Front Physiol 2017; 8:722. [PMID: 28983255 PMCID: PMC5613147 DOI: 10.3389/fphys.2017.00722] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 09/06/2017] [Indexed: 12/16/2022] Open
Abstract
HIGHLIGHTS
The aim of the research was to determine the functional effects and molecular mechanisms of GABAB receptor on ischemia reperfusion-induced gastric injury in rats. The lateral hypothalamus area GABAB receptor attenuated the ischemia reperfusion-induced gastric injury by up-regulating the production of GABA, GABABR, and down-regulating P-GABABR in the brain. This work would provide a new therapeutic strategy for acute gastric injury. Gastric ischemia-reperfusion (GI-R) injury progression is largely associated with excessive activation of the greater splanchnic nerve (GSN). This study aims to investigate the protective effects of GABAB receptor (GABABR) in the lateral hypothalamic area (LHA) on GI-R injury. A model of GI-R injury was established by clamping the celiac artery for 30 min and then reperfusion for 1 h. The coordinate of FN and LHA was identified in Stereotaxic Coordinates and then the L-Glu was microinjected into FN, GABAB receptor agonist baclofen, or GABAB receptor antagonist CGP35348 was microinjected into the LHA, finally the GI-R model was prepared. The expression of GABABR, P-GABABR, NOX2, NOX4, and SOD in the LHA was detected by western blot, PCR, and RT-PCR. The expression of IL-1β, NOX2, and NXO4 in gastric mucosa was detected by western blot. We found that microinjection of L-Glu into the FN or GABAB receptor agonist (baclofen) into the LHA attenuated GI-R injury. Pretreatment with GABAB receptor antagonist CGP35348 reversed the protective effects of FN stimulation or baclofen into the LHA. Microinjection of baclofen into the LHA obviously reduced the expression of inflammatory factor IL-1β, NOX2, and NOX4 in the gastric mucosa. Conclusion: The protective effects of microinjection of GABABR agonist into LHA on GI-R injury in rats could be mediated by up-regulating the production of GABA, GABABR, and down-regulating P-GABABR in the LHA.
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Affiliation(s)
- Lin Gao
- Neurology Center, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou, China
| | - Huiru Zhao
- Shanghai Key Laboratory of Bio-Crops, College of Life Science, Shanghai UniversityShanghai, China
| | - Tao Zhu
- Department of Life Science, Heze UniversityHeze, China
| | - Yeliu Liu
- Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical UniversityHuai'an, China
| | - Li Hu
- Shanghai Key Laboratory of Bio-Crops, College of Life Science, Shanghai UniversityShanghai, China
| | - Zhenguo Liu
- Shanghai Key Laboratory of Bio-Crops, College of Life Science, Shanghai UniversityShanghai, China
| | - Hai Huang
- Shanghai Key Laboratory of Bio-Crops, College of Life Science, Shanghai UniversityShanghai, China
| | - Fuxue Chen
- Shanghai Key Laboratory of Bio-Crops, College of Life Science, Shanghai UniversityShanghai, China
| | - Zhenxu Deng
- Department of Life Science, Heze UniversityHeze, China
| | - Dechang Chu
- Department of Life Science, Heze UniversityHeze, China
| | - Dongshu Du
- Neurology Center, The First Affiliated Hospital of Zhengzhou UniversityZhengzhou, China.,Shanghai Key Laboratory of Bio-Crops, College of Life Science, Shanghai UniversityShanghai, China
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Love MR, Palee S, Chattipakorn SC, Chattipakorn N. Effects of electrical stimulation on cell proliferation and apoptosis. J Cell Physiol 2017; 233:1860-1876. [PMID: 28452188 DOI: 10.1002/jcp.25975] [Citation(s) in RCA: 93] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Accepted: 04/24/2017] [Indexed: 02/06/2023]
Abstract
The application of exogenous electrical stimulation (ES) to cells in order to manipulate cell apoptosis and proliferation has been widely investigated as a possible method of treatment in a number of diseases. Alteration of the transmembrane potential of cells via ES can affect various intracellular signaling pathways which are involved in the regulation of cellular function. Controversially, several types of ES have proved to be effective in both inhibiting or inducing apoptosis, as well as increasing proliferation. However, the mechanisms through which ES achieves this remain fairly unclear. The aim of this review was to comprehensively summarize current findings from in vitro and in vivo studies on the effects of different types of ES on cell apoptosis and proliferation, highlighting the possible mechanisms through which ES induced these effects and define the optimum parameters at which ES can be used. Through this we hope to provide a greater insight into how future studies can most effectively use ES at the clinical trial stage.
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Affiliation(s)
- Maria R Love
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Siripong Palee
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
| | - Siriporn C Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.,Department of Oral Biology and Diagnostic Science, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
| | - Nipon Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.,Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Han H, Yang J, Fei S, Liu Z, Zhu S, Dong Q, Gao Z, Wang S, Zhang J. Protective effect of carbachol postconditioning on hypoxia/reoxygenation-induced injury in human gastric epithelial cells. Life Sci 2016; 144:234-42. [DOI: 10.1016/j.lfs.2015.11.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Revised: 11/22/2015] [Accepted: 11/28/2015] [Indexed: 02/07/2023]
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Gao L, Zhu T, Xie G, Lou X, Li S, Zhou Y, Deng Z, Chu D, Lou J, Du D. GABA(A) receptor overexpression in the lateral hypothalamic area attenuates gastric ischemia‑reperfusion injury in rats. Mol Med Rep 2014; 11:1057-62. [PMID: 25354809 DOI: 10.3892/mmr.2014.2816] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Accepted: 08/22/2014] [Indexed: 11/05/2022] Open
Abstract
Excessive activation of the greater splanchnic nerve (GSN) has previously been determined to contribute to the progression of gastric ischemia‑reperfusion (GI‑R) injury. The present study was designed to estimate the protective effects of GABAA receptor (GABA(A)R) overexpression in the lateral hypothalamic area (LHA) against GI‑R injury. The GI‑R injury model was induced in rats by clamping the celiac artery for 30 min and then reperfusing for 1 h. Microinjection of recombinant adenoviral vectors overexpressing GABA(A)R (Ad‑GABA(A)R) or control adenoviral vectors (Ad‑Con) into the LHA was conducted in GI‑R and normal control rats. Significant protective effects were observed on day 2 after Ad‑GABA(A)R treatment in the GI‑R injury rats. Ad‑GABA(A)R treatment reduced plasma norepinephrine levels, plasma angiotensin II levels and peripheral GSN activity, but increased the gastric mucosal blood flow, as compared with Ad‑Con treatment. These results indicate that adenoviral vector‑induced GABA(A)R overexpression in the LHA blunts GSN activity and subsequently alleviates the effects of gastric injury in GI‑R rats.
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Affiliation(s)
- Lin Gao
- Department of Neurology, The Affiliated Second Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China
| | - Tao Zhu
- Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, P.R. China
| | - Guilin Xie
- Life Science College of Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China
| | - Xiangxin Lou
- Department of Bioengineering, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, P.R. China
| | - Shibao Li
- Department of Laboratory Medicine, Lianyungang Hospital Affiliated Bengbu Medical College, Lianyungang, Jiangsu 222006, P.R. China
| | - Yan Zhou
- Department of Laboratory Medicine, Lianyungang Hospital Affiliated Bengbu Medical College, Lianyungang, Jiangsu 222006, P.R. China
| | - Zhenxu Deng
- Department of Life Science, Heze University, Heze, Shandong 274500, P.R. China
| | - Dechang Chu
- Department of Life Science, Heze University, Heze, Shandong 274500, P.R. China
| | - Jiyu Lou
- Department of Neurology, The Affiliated Second Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China
| | - Dongshu Du
- Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, P.R. China
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Wang T, Zhou YT, Chen XN, Zhu AX, Wu BH. Remote ischemic postconditioning protects against gastric mucosal lesions in rats. World J Gastroenterol 2014; 20:9519-9527. [PMID: 25071347 PMCID: PMC4110584 DOI: 10.3748/wjg.v20.i28.9519] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Revised: 01/21/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the protective effects of remote ischemic postconditioning (RIP) against limb ischemia-reperfusion (IR)-induced gastric mucosal injury.
METHODS: Gastric IR was established in male Wistar rats by placing an elastic rubber band under a pressure of 290-310 mmHg on the proximal part of both lower limbs for 3 h followed by reperfusion for 0, 1, 3, 6, 12 or 24 h. RIP was performed using three cycles of 30 s of reperfusion and 30 s of reocclusion of the femoral aortic immediately after IR and before reperfusion for up to 24 h. Rats were randomly assigned to receive IR (n = 36), IR followed by RIP (n = 36), or sham treatment (n = 36). Gastric tissue samples were collected from six animals in each group at each timepoint and processed to determine levels of malondialdehyde (MDA), superoxide dismutase (SOD), xanthine oxidase (XOD) and myeloperoxidase (MPO). Additional samples were processed for histologic analysis by hematoxylin and eosin staining. Blood samples were similarly collected to determine serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), tumor necrosis factor (TNF)-α and interleukin (IL)-10.
RESULTS: The pathologic changes in gastric tissue induced by IR were observed by light microscopy. Administration of RIP dramatically reduced the gastric damage score after 6 h of reperfusion (5.85 ± 0.22 vs 7.72 ± 0.43; P < 0.01). In addition, RIP treatment decreased the serum activities of LDH (3.31 ± 0.32 vs 6.46 ± 0.03; P < 0.01), CK (1.94 ± 0.20 vs 4.54 ± 0.19; P < 0.01) and the concentration of TNF-α (53.82 ± 0.85 vs 88.50 ± 3.08; P < 0.01), and elevated the concentration of IL-10 (101.46 ± 5.08 vs 99.77 ± 4.32; P < 0.01) induced by IR at 6 h. Furthermore, RIP treatment prevented the marked elevation in MDA (3.79 ± 0.29 vs 6.39 ± 0.81) content, XOD (7.81 ± 0.75 vs 10.37 ± 2.47) and MPO (0.47 ± 0.05 vs 0.82 ± 0.03) activities, and decrease in SOD (4.95 ± 0.32 vs 3.41 ± 0.38; P < 0.01) activity in the gastric tissue as measured at 6 h.
CONCLUSION: RIP provides effective functional protection and prevents cell injury to gastric tissue induced by limb IR via anti-inflammatory and antioxidant actions.
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Du DS, Zhu T, Ren ST, Xie GL, Li SB, Chu DC, Liu XT, Liu M, Ma XB, Zhou MH, Zhu DN, Deng ZX, Wang J. γ-Aminobutyric acid-mediated neurotransmission in cerebellar-hypothalamic circuit attenuates gastric mucosal injury induced by ischemia-reperfusion. Neurogastroenterol Motil 2013; 25:313-e249. [PMID: 23279161 DOI: 10.1111/nmo.12062] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Excessive greater splanchnic nerve (GSN) activation contributes to the progression of gastric ischemia-reperfusion (GI-R) injury. This study was designed to investigate the protective mechanism of cerebellar fastigial nucleus (FN) stimulation against GI-R injury. METHODS The GI-R injury model was induced in rats by clamping the celiac artery for 30 min, and then reperfusion for 30 min, 1, 3, 6, or 24 h, respectively. KEY RESULTS Microinjection of L-Glu (3, 6, 12 μg) into the FN dose-dependently attenuated GI-R injury and GSN activity. In addition, there was an enhancement of gastric mucosal blood flow in GI-R rats. Pretreatment with the glutamic acid decarboxylase antagonist into the FN, the GABAA receptor antagonist into the lateral hypothalamic area or lesion of superior cerebellar peduncle all reversed the protective effects of the FN stimulation. Furthermore, the FN stimulation reduced the TUNEL-positive gastric mucosal cell and Bax-positive gastric mucosal cell in GI-R rats. CONCLUSIONS & INFERENCES These results indicate that the protective effects of the FN stimulation against GI-R injury may be mediated by attenuation of the excessive GSN activation, gastric mucosal cell apoptosis, and Bax expression in GI-R rats.
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Affiliation(s)
- D S Du
- Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, Shanghai, China
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Takahashi T, Steinberg GK, Zhao H. Phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 may not always represent its kinase activity in a rat model of focal cerebral ischemia with or without ischemic preconditioning. Neuroscience 2012; 209:155-60. [PMID: 22366512 DOI: 10.1016/j.neuroscience.2012.02.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2011] [Revised: 01/31/2012] [Accepted: 02/04/2012] [Indexed: 11/15/2022]
Abstract
The extracellular signal-regulated kinase (ERK) 1/2 protein requires a dual phosphorylation at conserved threonine and tyrosine residues to be fully activated under normal physiological conditions. Thus, ERK1/2 kinase activity is often defined by the quantity of phosphorylated kinase. However, this may not accurately represent its true activity under certain pathological conditions. We investigated whether ERK1/2 kinase activity is proportional to its phosphorylation state in a rat focal ischemia model with and without rapid ischemic preconditioning. We showed that phosphorylated-ERK1/2 protein levels were increased 2.6±0.07-fold, and ERK1/2 kinase activity was increased 10.6±1.9-fold in animals receiving ischemic preconditioning alone without test ischemia compared with sham group (P<0.05, n=6/group), suggesting that phosphorylated-ERK1/2 protein levels represent its kinase activity under these conditions. However, preconditioning plus test ischemia robustly blocked ERK1/2 kinase activity, whereas it increased phosphorylated-ERK1/2 protein levels beyond those receiving test ischemia alone, suggesting that phosphorylated-ERK1/2 protein levels were not representative of actual kinase activity in this pathological condition. In conclusion, protein phosphorylation levels of ERK1/2 do not always correspond to kinase activity, thus, measuring the true kinase activity is essential.
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Affiliation(s)
- T Takahashi
- Department of Neurosurgery and Stanford Stroke Center, Stanford University, Stanford, CA, USA
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Guo F, Xu L, Sun X, Gao S, Zhu H. The paraventricular nucleus modulates thyroidal motilin release and rat gastric motility. J Neuroendocrinol 2011; 23:767-77. [PMID: 21756270 DOI: 10.1111/j.1365-2826.2011.02190.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Motilin, an important endocrine regulator of gastrointestinal motility, was once considered to be produced in the gastrointestinal tract and brain. In recent years, however, motilin has been found in the human thyroid, as well as in that of the guinea pig. The physiological function and central modulation of thyroidal motilin remain poorly understood. To determine the functional role of thyroidal motilin, we observed the concentration of motilin in the plasma and also gastric motility before and after thyroidectomy. Our studies show that both the concentration of plasma motilin and gastric motility were decreased after thyroidectomy. To explore modulation-related nuclei, a c-Fos immune response experiment was carried out. The PVN of the hypothalamus was the main area of reactivity after thyroidectomy. Subsequently, we studied the effects of electrical excitation and PVN lesions on gastric motility and the expression of motilin in the thyroid and plasma. Excitation of the PVN was shown to prompt gastric motility that was partly prevented by the motilin receptor antagonist, GM-109. The effects of PVN excitation on gastric contraction were significantly reduced in thyroidectomised rats. In addition, the expression of motilin in the thyroid was significantly increased after PVN excitation and decreased after PVN lesions. The changes in the concentration of motilin in plasma induced by PVN stimulation were positively correlated with changes of gastric motility. In our in vitro study, the motilin secreted from TT cells (a parafollicular cell line originating from human thyroid medullary carcinoma) gradually increased on day 6 of culture, and motilin and calcitonin (CT) were co-expressed in TT cells. These results demonstrate that motilin from the thyroid could be secreted into the peripheral plasma and affect gastric motility and that PVN was a central nucleus for modulating gastric motility and motilin expression in the thyroid.
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Affiliation(s)
- F Guo
- Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, China
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Wang T, Leng YF, Zhang Y, Xue X, Kang YQ, Zhang Y. Oxidative stress and hypoxia-induced factor 1α expression in gastric ischemia. World J Gastroenterol 2011; 17:1915-22. [PMID: 21528068 PMCID: PMC3080729 DOI: 10.3748/wjg.v17.i14.1915] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2010] [Revised: 12/10/2010] [Accepted: 12/17/2010] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the relation of reactive oxygen species (ROS) to hypoxia induced factor 1α (HIF-1α) in gastric ischemia.
METHODS: The animal model of gastric ischemia reperfusion was established by placing an elastic rubber band on the proximal part of the bilateral lower limb for ligature for 3 h and reperfusion for 0, 1, 3, 6, 12 or 24 h. Ischemic post-conditioning, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were conducted before reperfusion. Histological and immunohistochemical methods were used to assess the gastric oxidative damageand the expression of HIF1-α in gastric ischemia. The malondialdehyde (MDA) content and superoxide dismutase (SOD), xanthine oxidase (XOD) and myeloperoxidase (MPO) activities were determined by colorimetric assays.
RESULTS: Ischemic post-conditioning can reduce post-ischemic oxidativestressand the expression of HIF-1α of gastric tissue resulting from limb ischemia reperfusion injury. MDA, SOD, XOD and MPO were regarded as indexes for mucosal injuries from ROS, and ROS was found to affect the expression of HIF-1α under gastric ischemic conditions.
CONCLUSION: ROS affects HIF-1α expression under gastric ischemic conditions induced by limb ischemia reperfusion injury. Therefore, ROS can regulate HIF-1α expression in gastric ischemia.
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Gao L, Fei S, Qiao W, Zhang J, Xing H, Du D. Protective effect of chemical stimulation of cerebellar fastigial nucleus on stress gastric mucosal injury in rats. Life Sci 2011; 88:871-8. [PMID: 21419784 DOI: 10.1016/j.lfs.2011.03.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2010] [Revised: 02/23/2011] [Accepted: 03/11/2011] [Indexed: 12/16/2022]
Abstract
AIMS We investigated the protective effects of chemical stimulation of cerebellar fastigial nucleus (FN) on stress gastric mucosal injury (SGMI) and its possible neuro-regulatory mechanisms in rats. MAIN METHODS Chemical stimulation, electrical stimulation, chemical ablation, electrolytic lesion, and microinjection were used to investigate the effects of FN simulation on SGMI. The model of SGMI was established by restraint and water (21±1°C)-immersion (RWI) for 3h in rats. The gastric mucosal injury index indicated the severity of gastric mucosal injuries. KEY FINDINGS We showed that microinjection of L-glutamic acid into the FN or electrical stimulation of the FN markedly attenuated SGMI. Either chemical lesion of the FN or electrical ablation of the decussation of superior cerebellar peduncle (DSCP) obviously aggravated SGMI. The protective effect of FN stimulation on SGMI was reversed after chemical ablation of the lateral hypothalamic area (LHA). The protective effect of FN was prevented by pretreatment with the glutamic acid decarboxylase antagonist, 3-MPA into the FN or GABA(A) receptor antagonist, bicuculline into the LHA. The protective effect of FN was abolished by pretreatment with sympathectomy. The discharge frequency of greater splanchnic nerve (GSN) was decreased and gastric mucosal blood flow (GMBF) was increased after chemical stimulation of FN. These results indicate that the FN participates in regulation of SGMI, and is a specific area in the CNS for exerting protective effects on the SGMI. The DSCP, LHA and peripheral sympathetic nerve may be involved in this process. SIGNIFICANCE Our findings might provide a new and improved understanding of the cerebellar function and an effective treatment strategy for stress gastric mucosal injury.
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Affiliation(s)
- Ling Gao
- Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical College 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China
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Du D, Ma X, Zhang J, Zhang Y, Zhou X, Li Y. Cellular and molecular mechanisms of 17beta-estradiol postconditioning protection against gastric mucosal injury induced by ischemia/reperfusion in rats. Life Sci 2009; 86:30-8. [PMID: 19931544 DOI: 10.1016/j.lfs.2009.11.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2009] [Revised: 10/29/2009] [Accepted: 10/30/2009] [Indexed: 12/15/2022]
Abstract
AIMS To investigate the protective effects of 17beta-estradiol postconditioning against ischemia/reperfusion (I-R)-induced gastric mucosal injury in rats. MAIN METHODS The animal model of gastric ischemia/reperfusion was established by clamping of the celiac artery for 30 min and reperfusion for 30 min, 1h, 3h, 6h, 12h or 24h. 17beta-estradiol at doses of 5, 50 or 100 microg/kg (rat) was administered via peripheral veins 2 min before reperfusion. In a subgroup of rats, the estrogen receptor antagonist fulvestrant (Ful, 2mg/kg) was intravenously injected prior to 17beta-estradiol administration. Histological and immunohistochemical methods were employed to assess the gastric mucosal injury index and gastric mucosal cell apoptosis and proliferation. The malondialdehyde (MDA) concentration, superoxide dismutase (SOD) activity, xanthine oxidase (XOD) activity and hydroxyl free radical (-OH) inhibitory ability were determined by colorimetric assays. Subsequently, the expression of Bcl-2 and Bax in rat gastric mucosa was examined by western blotting. KEY FINDINGS 17beta-estradiol dose-dependently inhibited gastric I-R (GI-R) injury, and 17beta-estradiol (50 microg/kg) markedly attenuated GI-R injury 1h after reperfusion. 17beta-estradiol inhibited gastric mucosal cell apoptosis and promoted gastric mucosal cell proliferation in addition to increasing SOD activity and -OH inhibitory ability and decreasing the MDA content and XOD activity. The Bax protein level increased 1h after GI-R and was markedly reduced by intravenous administration of 17beta-estradiol. In contrast, the level of Bcl-2 protein decreased 1h after GI-R and was restored to normal levels by intravenous administration of 17beta-estradiol. These effects of 17beta-estradiol were inhibited by pretreatment with fulvestrant. SIGNIFICANCE 17beta-estradiol postconditioning should be investigated further as a possible strategy against gastric mucosal injury.
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Affiliation(s)
- Dongshu Du
- Department of Physiology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou 221002, Jiangsu Province, China
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Zhang YM, Zhang WW, Zhang JF. JNK mediates the effects of oxytocin microinjected into the paraventricular nucleus on gastric ischemia-reperfusion in rats. Shijie Huaren Xiaohua Zazhi 2009; 17:1919-1924. [DOI: 10.11569/wcjd.v17.i19.1919] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the molecular mechanism underlying the role of JNK in mediating the effects of oxytocin (OT) microinjected into the paraventricular nucleus (PVN) on gastric ischemia-reperfusion (GI-R) injury.
METHODS: Sprague-Dawley (SD) rats were randomly divided into four groups: vehicle group, OT group, atosiban group and OT plus atosiban group. GI-R injury was induced in rats by clamping the celiac artery for 30 min and then reperfusing for 1 h. A cannula was inserted into the unilateral PVN for microinjection of OT. The expression of p-JNK, Bax and Bcl-2 proteins in rat gastric mucosa was examined by Western blot and immunohistochemistry.
RESULTS: Compared with the vehicle group, microinjection of OT (600 ng) into PVN significantly decreased the expression of p-JNK and Bax proteins but increased the expression of Bcl-2 protein in gastric mucosa following GI-R (all P < 0.01). Pre-administration of atosiban (an OT receptor antagonist) into the lateral cerebral ventricle could prevent the effects of OT (F = 56.33, P < 0.01; F = 145.2, P < 0.01, F = 49.32, P < 0.01), increase the expression of p-JNK and Bax proteins, and decrease the expression of Bcl-2 protein when compared with the OT group.
CONCLUSION: Microinjection of OT into PVN attenuates GI-R injury through down-regulation of p-JNK protein, which in turn leads to a decrease in Bax expression and an increase in Bcl-2 expression.
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The role of nuclear factor-kappaB in the effect of angiotensin II in the paraventricular nucleus in protecting the gastric mucosa from ischemia-reperfusion injury in rats. J Gastroenterol 2009; 43:687-98. [PMID: 18807130 DOI: 10.1007/s00535-008-2217-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2007] [Accepted: 05/12/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND The purpose of this study was to elucidate the role of nuclear factor kappaB (NF-kappaB) in the development of gastric ischemia-reperfusion (GI-R) injury and in mediating the effects of angiotensin II (Ang II) in the paraventricular nucleus (PVN) on GI-R injury. METHODS GI-R injury was induced in rats by clamping the celiac artery for 30 min and then reperfusing for 1 h. A cannula was inserted into the unilateral PVN for microinjection of Ang II. The expressions and levels of NF-kappaB (p65), IkappaB-alpha, and phosphorylated IkappaB-alpha in rat gastric mucosa were examined by Western blotting and immunohistochemistry. A laser Doppler flowmeter was used to assess gastric blood flow (GBF). Malondialdehyde (MDA) was determined using the thiobarbituric acid (TBA) method, and superoxide dismutase (SOD) activity was determined by the xanthine/xanthine oxidase method. RESULTS Microinjection of Ang II (3, 30, and 300 ng) into the PVN dose-dependently inhibited GI-R injury. The levels and expressions of NF-kappaB (p65) and phosphospecific IkappaB-alpha protein increased 1 h after GI-R and were markedly reduced by microinjection of Ang II into the PVN. In contrast, the level and expression of IkappaB-alpha protein decreased 1 h after ischemia-reperfusion and recovered to the normal level by microinjection of Ang II into the PVN. The effects of Ang II were prevented by pretreatment with the Ang II AT1 receptor antagonist losartan (5 microg) microinjected into the lateral cerebral ventricle. Inhibition of NF-kappaB activity by pyrrolidine dithiocarbamate (PDTC, 200 mg/kg) produced similar effects in rats subjected to ischemia-reperfusion with or without microinjection of Ang II into the PVN. Administration of PDTC attenuated gastric mucosal injury and suppressed the activation of NF-kappaB (p65). Ang II microinjection into the PVN increased GBF and decreased the MDA content but did not alter SOD activity in the gastric mucosa following ischemia-reperfusion. CONCLUSIONS NF-kappaB plays a role in PVN Ang II-mediated protection against GI-R injury. These central effects of Ang II are mediated by AT1 receptors.
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Zhang YM, Zhang JF, Yan CD. Capsaicin-sensitive afferent fibers mediate the protective effect of electrical stimulation of paraventricular nucleus against gastric ischemia-reperfusion injury in rats. Shijie Huaren Xiaohua Zazhi 2008; 16:3616-3620. [DOI: 10.11569/wcjd.v16.i32.3616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To elucidate the role of capsaicin-sensitive afferent fibers in mediating the effect of electrical stimulation (ES) of paraventricular nucleus (PVN) against rat gastric ischemia-reperfusion (GI-R) injury.
METHODS: GI-R injury was induced in rats by clamping the celiac artery for 30 min and then reperfusing for 1 h. The methods of nuclear electric stimulation to excite the PVN and pretreatment with a high dose of capsaicin to ablate the capsaicin-sensitive afferent fibers were used to explore the role of capsaicin-sensitive afferent fibers in the regulation of PVN on GI-R injury.
RESULTS: Pretreament with a high dose of capsaicin to ablate afferent fibers partly abolished the protective effect of PVN against GI-R injury and the injury was increased by 54.85% as compared with that in the PVN stimulation group (P < 0.01); Pretreament with L-nitro-L-arginine methyl ester (L-NAME) significantly abolished the protective effect of PVN against GI-R injury and the injury was increased by 72.98% as compared with that in the PVN stimulation group (P < 0.01).
CONCLUSION: Capsaicin-sensitive afferent fibers and endogenous NO are involved in the protective effect of PVN stimulation against GI-R injury.
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Zhang YM, Wei EQ, Hu X, Xu M, Shi Y, Zhang JF. Administration of angiotensin II in the paraventricular nucleus protects gastric mucosa from ischemia-reperfusion injury. Brain Res 2008; 1212:25-34. [PMID: 18445492 DOI: 10.1016/j.brainres.2008.03.028] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2007] [Revised: 03/09/2008] [Accepted: 03/13/2008] [Indexed: 12/14/2022]
Abstract
Our previous study demonstrated that electrical stimulation of the hypothalamic paraventricular nucleus (PVN) protects against gastric ischemia-reperfusion (GI-R) injury, but it is still unknown whether angiotensin II (Ang II) in the PVN plays a role in the development of GI-R. The purpose of this study was to investigate the effect of Ang II in the PVN on GI-R injury. GI-R injury was induced in rats by clamping the celiac artery for 30 min, and then reperfusing for 30 min, 1 h, 3 h, 6 h or 24 h, respectively. A cannula was inserted into the unilateral PVN for microinjection of Ang II. The extent of gastric mucosal damage was determined by gross and histological methods. We found that microinjection of pharmacological doses of Ang II (3, 30, and 300 ng) into the PVN dose-dependently inhibited GI-R injury, and that Ang II (30 ng) markedly attenuated GI-R injury at 1 h and 3 h after reperfusion. The effect of Ang II was prevented by pretreatment with the Ang II AT1 receptor antagonist losartan (5 microg) into the lateral cerebral ventricle. Furthermore, the protective effect of Ang II on GI-R injury was abolished by propranolol (1 mg/kg, i.v.) or disconnection of the nerves innervating the adrenal glands, was augmented by sympathectomy or phentolamine (1 mg/kg, i.v.), and was not affected by subdiaphragmatic vagotomy or atropine (1 mg/kg, i.v.). These results indicate that the PVN is a responsive site for central Ang II-induced protection against GI-R injury. The central effects of Ang II are mediated by AT1 receptors in the PVN, and the peripheral effects by a sympathetic-adrenal gland/beta-adrenoceptor pathway.
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Affiliation(s)
- Yong-Mei Zhang
- Department of Pharmacology, School of Medicine, Zhejiang University, 388, Yu Hang Tang Road, Hangzhou 310058, China
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