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Durcan C, Hossain M, Chagnon G, Perić D, Girard E. Characterization of the layer, direction and time-dependent mechanical behaviour of the human oesophagus and the effects of formalin preservation. J R Soc Interface 2024; 21:20230592. [PMID: 38593841 PMCID: PMC11003784 DOI: 10.1098/rsif.2023.0592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 03/05/2024] [Indexed: 04/11/2024] Open
Abstract
The mechanical characterization of the oesophagus is essential for applications such as medical device design, surgical simulations and tissue engineering, as well as for investigating the organ's pathophysiology. However, the material response of the oesophagus has not been established ex vivo in regard to the more complex aspects of its mechanical behaviour using fresh, human tissue: as of yet, in the literature, only the hyperelastic response of the intact wall has been studied. Therefore, in this study, the layer-dependent, anisotropic, visco-hyperelastic behaviour of the human oesophagus was investigated through various mechanical tests. For this, cyclic tests, with increasing stretch levels, were conducted on the layers of the human oesophagus in the longitudinal and circumferential directions and at two different strain rates. Additionally, stress-relaxation tests on the oesophageal layers were carried out in both directions. Overall, the results show discrete properties in each layer and direction, highlighting the importance of treating the oesophagus as a multi-layered composite material with direction-dependent behaviour. Previously, the authors conducted layer-dependent cyclic experimentation on formalin-embalmed human oesophagi. A comparison between the fresh and embalmed tissue response was carried out and revealed surprising similarities in terms of anisotropy, strain-rate dependency, stress-softening and hysteresis, with the main difference between the two preservation states being the magnitude of these properties. As formalin fixation is known to notably affect the formation of cross-links between the collagen of biological materials, the differences may reveal the influence of cross-links on the mechanical behaviour of soft tissues.
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Affiliation(s)
- Ciara Durcan
- Zienkiewicz Institute for Modelling, Data and Artificial Intelligence, Faculty of Science and Engineering, Swansea University, Swansea SA1 8EN, UK
- CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, Grenoble Alpes University, Grenoble 38000, France
| | - Mokarram Hossain
- Zienkiewicz Institute for Modelling, Data and Artificial Intelligence, Faculty of Science and Engineering, Swansea University, Swansea SA1 8EN, UK
| | - Grégory Chagnon
- CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, Grenoble Alpes University, Grenoble 38000, France
| | - Djordje Perić
- Zienkiewicz Institute for Modelling, Data and Artificial Intelligence, Faculty of Science and Engineering, Swansea University, Swansea SA1 8EN, UK
| | - Edouard Girard
- CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, Grenoble Alpes University, Grenoble 38000, France
- Laboratoire d’Anatomie des Alpes Françaises, Grenoble Alpes University, Grenoble, France
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Durcan C, Hossain M, Chagnon G, Perić D, Girard E. Mechanical experimentation of the gastrointestinal tract: a systematic review. Biomech Model Mechanobiol 2024; 23:23-59. [PMID: 37935880 PMCID: PMC10901955 DOI: 10.1007/s10237-023-01773-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 09/10/2023] [Indexed: 11/09/2023]
Abstract
The gastrointestinal (GI) organs of the human body are responsible for transporting and extracting nutrients from food and drink, as well as excreting solid waste. Biomechanical experimentation of the GI organs provides insight into the mechanisms involved in their normal physiological functions, as well as understanding of how diseases can cause disruption to these. Additionally, experimental findings form the basis of all finite element (FE) modelling of these organs, which have a wide array of applications within medicine and engineering. This systematic review summarises the experimental studies that are currently in the literature (n = 247) and outlines the areas in which experimentation is lacking, highlighting what is still required in order to more fully understand the mechanical behaviour of the GI organs. These include (i) more human data, allowing for more accurate modelling for applications within medicine, (ii) an increase in time-dependent studies, and (iii) more sophisticated in vivo testing methods which allow for both the layer- and direction-dependent characterisation of the GI organs. The findings of this review can also be used to identify experimental data for the readers' own constitutive or FE modelling as the experimental studies have been grouped in terms of organ (oesophagus, stomach, small intestine, large intestine or rectum), test condition (ex vivo or in vivo), number of directions studied (isotropic or anisotropic), species family (human, porcine, feline etc.), tissue condition (intact wall or layer-dependent) and the type of test performed (biaxial tension, inflation-extension, distension (pressure-diameter), etc.). Furthermore, the studies that investigated the time-dependent (viscoelastic) behaviour of the tissues have been presented.
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Affiliation(s)
- Ciara Durcan
- Zienkiewicz Centre for Modelling, Data and AI, Faculty of Science and Engineering, Swansea University, Swansea, SA1 8EN, UK
- Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
| | - Mokarram Hossain
- Zienkiewicz Centre for Modelling, Data and AI, Faculty of Science and Engineering, Swansea University, Swansea, SA1 8EN, UK.
| | - Grégory Chagnon
- Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
| | - Djordje Perić
- Zienkiewicz Centre for Modelling, Data and AI, Faculty of Science and Engineering, Swansea University, Swansea, SA1 8EN, UK
| | - Edouard Girard
- Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
- Laboratoire d'Anatomie des Alpes Françaises, Université Grenoble Alpes, Grenoble, France
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Yang X, Zhao J, Li H, Pan L, Guo J, Li J, Zhang Y, Chen P, Li P. Effect of Tangshen formula on the remodeling of small intestine and colon in Zucker diabetic fatty rats. Heliyon 2023; 9:e21007. [PMID: 37886764 PMCID: PMC10597860 DOI: 10.1016/j.heliyon.2023.e21007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 09/28/2023] [Accepted: 10/12/2023] [Indexed: 10/28/2023] Open
Abstract
Background and aim Previous study have demonstrated that Tangshen Formula (TSF) could attenuate colonic histomorphological remodeling in the diabetic rat model induced by high fat diet plus low dosage streptozotocin (STZ). However, it is not clear whether TSF has same effect on small intestine and the effect on biomechanical properties of bowel. The aim of this study is to investigate the effect of TSF on histomorphological and biomechanical remodeling of small intestine and colon by using Zucker Diabetic Fatty (ZDF) Rat model. Materials and methods ZDF rats (obese fa/fa) with blood glucose higher than 11.7 mmol/L were divided into ZDF group (diabetic control group) and ZDF + TSF group (TSF treatment group), the later were intragastrically administered TSF. The ZDF rats (lean fa/+) were served as normal control (ZL) group. The rats in the ZL and ZDF groups were administered with saline. The experimental period covered from 8 weeks to 24 weeks. At the end of experiment, the ileal and colonic segments were studied in vitro. The histomorphometry and biomechanical parameters were measured. Results Compared with ZL group histomorphologically, the wet weight per unit length, wall thickness, wall area and fractions of total and type I and type III collagen in different layers for both ileum and colon increased in ZDF group. Those increasing parameters were partially inhibited in ZDF + TSF group. Compared with ZL group biomechanically, ZDF and ZDF + TSF groups had smaller opening angle and residual strain in ileum, and bigger opening angle and residual strain in colon. Whereas the wall became softer in circumferential direction and stiffer in longitudinal direction for both ileum and colon. However, no difference of biomechanical parameters was found between ZDF and ZDF + TSF groups. Conclusion The histomorphological and biomechanical remodeling of ileum and colon were happened in ZDF rats (obese fa/fa). TSF could partly attenuate ileal and colonic histomorphological remodeling rather than biomechanical remodeling.
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Affiliation(s)
- Xin Yang
- Beijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing (100029), China
| | - Jingbo Zhao
- Anbiping (Chongqing) Pathological Diagnosis Center, Chongqing, China
| | - Hong Li
- Beijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing (100029), China
| | - Lin Pan
- Beijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing (100029), China
| | - Jing Guo
- Beijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing (100029), China
| | - Jing Li
- Beijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing (100029), China
| | - Yuting Zhang
- Beijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing (100029), China
| | - Pengmin Chen
- Beijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing (100029), China
| | - Ping Li
- Beijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing (100029), China
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Wei L, Ji L, Miao Y, Han X, Li Y, Wang Z, Fu J, Guo L, Su Y, Zhang Y. Constipation in DM are associated with both poor glycemic control and diabetic complications: Current status and future directions. Biomed Pharmacother 2023; 165:115202. [PMID: 37506579 DOI: 10.1016/j.biopha.2023.115202] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 07/15/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
Constipation is a major complications of diabetes mellitus. With the accelerating prevalence of diabetes worldwide and an aging population, there is considerable research interest regarding the altered function and structure of the gastrointestinal tract in diabetic patients. Despite current advances in hyperglycemic treatment strategies, the specific pathogenesis of diabetic constipation remains unknown. Patients with constipation, may be reluctant to eat regularly, which may worsen glycemic control and thus worsen symptoms associated with underlying diabetic bowel disease. This paper presents a review of the complex relationship between diabetes and constipation, exploring the morphological alterations and biomechanical remodeling associated with intestinal motility dysfunction, as well as alterations in intestinal neurons, cellular signaling pathways, and oxidative stress. Further studies focusing on new targets that may play a role in the pathogenesis of diabetic constipation may, provide new ideas for the development of novel therapies to treat or even prevent diabetic constipation.
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Affiliation(s)
- Luge Wei
- Tianjin University of Traditional Chinese Medicine, China.
| | - Lanqi Ji
- Tianjin University of Traditional Chinese Medicine, China
| | - Yulu Miao
- Tianjin University of Traditional Chinese Medicine, China
| | - Xu Han
- Tianjin University of Traditional Chinese Medicine, China
| | - Ying Li
- Tianjin University of Traditional Chinese Medicine, China
| | - Zhe Wang
- Tianjin University of Traditional Chinese Medicine, China
| | - Jiafeng Fu
- Tianjin University of Traditional Chinese Medicine, China
| | - Liuli Guo
- Tianjin University of Traditional Chinese Medicine, China
| | - Yuanyuan Su
- Tianjin University of Traditional Chinese Medicine, China
| | - Yanjun Zhang
- Tianjin University of Traditional Chinese Medicine, China; First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, China
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Klinge MW, Sutter N, Mark EB, Haase AM, Borghammer P, Schlageter V, Lund S, Fleischer J, Knudsen K, Drewes AM, Krogh K. Gastric Emptying Time and Volume of the Small Intestine as Objective Markers in Patients With Symptoms of Diabetic Enteropathy. J Neurogastroenterol Motil 2021; 27:390-399. [PMID: 34210904 PMCID: PMC8266501 DOI: 10.5056/jnm19195] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 03/13/2020] [Accepted: 12/19/2020] [Indexed: 12/15/2022] Open
Abstract
Background/Aims Patients with diabetes mellitus (DM) often suffer from gastrointestinal (GI) symptoms, but these correlate poorly to established objective GI motility measures. Our aim is to perform a detailed evaluation of potential measures of gastric and small intestinal motility in patients with DM type 1 and severe GI symptoms. Methods Twenty patients with DM and 20 healthy controls (HCs) were included. GI motility was examined with a 3-dimensional-Transit capsule, while organ volumes were determined by CT scans. Results Patients with DM and HCs did not differ with regard to median gastric contraction frequency (DM 3.0 contractions/minute [interquartile range {IQR}, 2.9-3.0]; HCs 2.9 [IQR, 2.8-3.1]; P = 0.725), amplitude of gastric contractions (DM 9 mm [IQR, 8-11]; HCs 11 mm (IQR, 9-12); P = 0.151) or fasting volume of the stomach wall (DM 149 cm3 [IQR, 112-187]; HCs 132 cm3 [IQR, 107-154]; P = 0.121). Median gastric emptying time was prolonged in patients (DM 3.3 hours [IQR, 2.6-4.6]; HCs 2.4 hours [IQR, 1.8-2.7]; P = 0.002). No difference was found in small intestinal transit time (DM 5 hours [IQR, 3.7-5.6]; HCs 4.8 hours [IQR, 3.9-6.0]; P = 0.883). However, patients with DM had significantly larger volume of the small intestinal wall (DM 623 cm3 [IQR, 487-766]; HCs 478 cm3 [IQR, 393-589]; P = 0.003). Among patients, 13 (68%) had small intestinal wall volume and 9 (50%) had gastric emptying time above the upper 95% percentile of HCs. Conclusion In our study, gastric emptying time and volume of the small intestinal wall appeared to be the best objective measures in patients with DM type 1 and symptoms and gastroenteropathy.
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Affiliation(s)
- Mette W Klinge
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark
| | - Nanna Sutter
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark
| | - Esben B Mark
- Mech-Sense, Department of Hepatology and Gastroenterology, and Department of Clinical Medicine, Aalborg University Hospital, Denmark
| | - Anne-Mette Haase
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark
| | - Per Borghammer
- Department of Nuclear Medicine and PET, Aarhus University Hospital, Denmark.,Department of Clinical Medicine, Aarhus University, Denmark
| | | | - Sten Lund
- Department of Internal Medicine and Endocrinology, Aarhus University Hospital, Denmark.,Steno Diabetes Center Aarhus, Denmark
| | - Jesper Fleischer
- Steno Diabetes Center Aarhus, Denmark.,Steno Diabetes Center Copenhagen, Denmark
| | - Karoline Knudsen
- Department of Nuclear Medicine and PET, Aarhus University Hospital, Denmark
| | - Asbjørn M Drewes
- Mech-Sense, Department of Hepatology and Gastroenterology, and Department of Clinical Medicine, Aalborg University Hospital, Denmark
| | - Klaus Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark.,Steno Diabetes Center Aarhus, Denmark
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Zhao M, Liao D, Zhao J. Diabetes-induced mechanophysiological changes in the small intestine and colon. World J Diabetes 2017; 8:249-269. [PMID: 28694926 PMCID: PMC5483424 DOI: 10.4239/wjd.v8.i6.249] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 04/05/2017] [Accepted: 05/05/2017] [Indexed: 02/05/2023] Open
Abstract
The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients.
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The Constraints, Construction, and Verification of a Strain-Specific Physiologically Based Pharmacokinetic Rat Model. J Pharm Sci 2017; 106:2826-2838. [PMID: 28495566 DOI: 10.1016/j.xphs.2017.05.003] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Revised: 04/20/2017] [Accepted: 05/02/2017] [Indexed: 11/20/2022]
Abstract
The use of in vitro-in vivo extrapolation (IVIVE) techniques, mechanistically incorporated within physiologically based pharmacokinetic (PBPK) models, can harness in vitro drug data and enhance understanding of in vivo pharmacokinetics. This study's objective was to develop a user-friendly rat (250 g, male Sprague-Dawley) IVIVE-linked PBPK model. A 13-compartment PBPK model including mechanistic absorption models was developed, with required system data (anatomical, physiological, and relevant IVIVE scaling factors) collated from literature and analyzed. Overall, 178 system parameter values for the model are provided. This study also highlights gaps in available system data required for strain-specific rat PBPK model development. The model's functionality and performance were assessed using previous literature-sourced in vitro properties for diazepam, metoprolol, and midazolam. The results of simulations were compared against observed pharmacokinetic rat data. Predicted and observed concentration profiles in 10 tissues for diazepam after a single intravenous (i.v.) dose making use of either observed i.v. clearance (CLiv) or in vitro hepatocyte intrinsic clearance (CLint) for simulations generally led to good predictions in various tissue compartments. Overall, all i.v. plasma concentration profiles were successfully predicted. However, there were challenges in predicting oral plasma concentration profiles for metoprolol and midazolam, and the potential reasons and according solutions are discussed.
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da Rosa CVD, Azevedo SCSF, Bazotte RB, Peralta RM, Buttow NC, Pedrosa MMD, de Godoi VAF, Natali MRM. Supplementation with L-Glutamine and L-Alanyl-L-Glutamine Changes Biochemical Parameters and Jejunum Morphophysiology in Type 1 Diabetic Wistar Rats. PLoS One 2015; 10:e0143005. [PMID: 26659064 PMCID: PMC4681705 DOI: 10.1371/journal.pone.0143005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 10/29/2015] [Indexed: 01/01/2023] Open
Abstract
We evaluated the effects of the supplementation with L-glutamine and glutamine dipeptide (GDP) on biochemical and morphophysiological parameters in streptozotocin-diabetic rats. For this purpose, thirty animals were distributed into six groups treated orally (gavage) during thirty days: non diabetic rats (Control) + saline, diabetic + saline; Control + L-glutamine (248 mg/kg), Diabetic + L-glutamine (248 mg/kg), Control + GDP (400 mg/kg), Diabetic + GDP (400 mg/kg). Diabetes was induced by an intravenous injection of streptozotocin (60 mg/kg) and confirmed by fasting glucose ≥ 200 mg/dL. Physiological parameters, i.e., body mass, food intake, blood glucose, water intake, urine and faeces were evaluated during supplementation. After the period of supplementation, the animals were euthanized. The blood was collected for biochemical assays (fructosamine, transaminases, lipid profile, total protein, urea, ammonia). Moreover, the jejunum was excised and stored for morphophysiological assays (intestinal enzyme activity, intestinal wall morphology, crypt proliferative index, number of serotoninergic cells from the mucosa, and vipergic neurons from the submucosal tunica). The physiological parameters, protein metabolism and intestinal enzyme activity did not change with the supplementation with L-glutamine or GDP. In diabetic animals, transaminases and fructosamine improved with L-glutamine and GDP supplementations, while the lipid profile improved with L-glutamine. Furthermore, both forms of supplementation promoted changes in jejunal tunicas and wall morphometry of control and diabetic groups, but only L-glutamine promoted maintenance of serotoninergic cells and vipergic neurons populations. On the other hand, control animals showed changes that may indicate negative effects of L-glutamine. Thus, the supplementation with L-glutamine was more efficient for maintaining intestinal morphophysiology and the supplementation with GDP was more efficient to the organism as a whole. Thus, we can conclude that local differences in absorption and metabolism could explain the differences between the supplementation with L-glutamine or GDP.
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Affiliation(s)
| | | | - Roberto B. Bazotte
- Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Paraná, Brazil
| | - Rosane M. Peralta
- Department of Biochemistry, State University of Maringá, Maringá, Paraná, Brazil
| | - Nilza C. Buttow
- Department of Morphological Sciences, State University of Maringá, Maringá, Paraná, Brazil
| | | | - Vilma A. F. de Godoi
- Department of Physiological Sciences, State University of Maringá, Maringá, Paraná, Brazil
| | - Maria Raquel M. Natali
- Department of Morphological Sciences, State University of Maringá, Maringá, Paraná, Brazil
- * E-mail: (MR)
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Liu GF, Zhao JB, Zhen Z, Sha H, Chen PM, Li M, Zhang JC, Yuan MZ, Gao W, Gregersen H, Tong XL. Effect of Tangweian Jianji on upper gastrointestinal remodeling in streptozotocin-induced diabetic rats. World J Gastroenterol 2012; 18:4875-84. [PMID: 23002359 PMCID: PMC3447269 DOI: 10.3748/wjg.v18.i35.4875] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2012] [Revised: 04/23/2012] [Accepted: 04/27/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of Tangweian Jianji (TWAJJ) on the biomechanical and morphometrical remodeling of the upper gastrointestinal tract in diabetic rats.
METHODS: Diabetes was induced in 27 rats by injecting streptozotocin (40 mg/kg body weight), the animals were then divided into three groups (n = 9 in each group), i.e., diabetic control (DM); high dose (10 g/kg, T1) and low dose (5 g/kg, T2). Another 10 rats acted as normal controls (Control). TWAJJ was administered by gavage once daily. Blood glucose and serum insulin levels were measured. Circumferential length, wall thickness and opening angle were measured from esophageal, duodenal, jejunal and ileal ring segments. The residual strain was calculated from the morphometric data. Step-wise distension was carried out on esophageal and jejunal segments. The obtained data on the length, diameter and pressure changes were then used to calculate the circumferential and longitudinal stresses and strains. Real-time reverse transcription polymerase chain reaction was used to detect the receptor of advanced glycation end-products (RAGE) mRNA level in jejunal tissues.
RESULTS: At the end of the experiment, the blood glucose level was significantly higher and the serum insulin level was significantly lower in DM, T1 and T2 groups than in the control group (Glucose: 30.23 ± 0.41 mmol/L, 27.48 ± 0.27 mmol/L and 27.84 ± 0.29 mmol/L vs 5.05 ± 0.04 mmol/L, P = 1.65 × 10-16, P = 5.89 × 10-19 and P = 1.63 × 10-18, respectively; Insulin: 1.47 ± 0.32 μg/L, 2.66 ± 0.44 μg/L, 2.03 ± 0.29 μg/L and 4.17 ± 0.54 μg/L, P = 0.0001, P = 0.029 and P = 0.025, respectively). However, these levels did not differ among the DM, T1 and T2 groups. The wet weight per unit length, wall thickness and opening angle of esophageal and intestinal segments in the DM group were significantly higher than those in the control group (from P = 0.009 to P = 0.004). These parameters in the T1 group were significantly lower than those in the DM group (wet weight, duodenum: 0.147 ± 0.003 g/cm vs 0.158 ± 0.001 g/cm, P = 0.047; jejunum, 0.127 ± 0.003 g/cm vs 0.151 ± 0.002 g/cm, P = 0.017; ileum, 0.127 ± 0.004 g/cm vs 0.139 ± 0.003 g/cm, P = 0.046; wall thickness, esophagus: 0.84 ± 0.03 mm vs 0.94 ± 0.02 mm, P = 0.014; duodenum: 1.27 ± 0.06 mm vs 1.39 ± 0.05 mm, P = 0.031; jejunum: 1.19 ± 0.07 mm vs 1.34 ± 0.04 mm, P = 0.047; ileum: 1.09 ± 0.04 mm vs 1.15 ± 0.03 mm, P = 0.049; opening angle, esophagus: 112.2 ± 13.2˚ vs 134.7 ± 14.7˚, P = 0.027; duodenum: 105.9 ± 12.3˚ vs 123.1 ± 13.1˚, P = 0.046; jejunum: 90.1 ± 15.4˚ vs 115.5 ± 13.3˚, P = 0.044; ileum: 112.9 ± 13.4˚ vs 136.1 ± 17.1˚, P = 0.035). In the esophageal and jejunal segments, the inner residual stain was significantly smaller and the outer residual strain was larger in the DM group than in the control group (P = 0.022 and P = 0.035). T1 treatment significantly restored this biomechanical alteration (P = 0.011 and P = 0.019), but T2 treatment did not. Furthermore, the circumferential and longitudinal stiffness of the esophageal and jejunal wall increased in the DM group compared with those in the control group. T1, but not T2 treatment, significantly decreased the circumferential wall stiffness in the jejunal segment (P = 0.012) and longitudinal wall stiffness in the esophageal segment (P = 0.023). The mRNA level of RAGE was significantly decreased in the T1 group compared to that in the DM group (P = 0.0069).
CONCLUSION: TWAJJ (high dose) treatment partly restored the morphometric and biomechanical remodeling of the upper gastrointestinal tract in diabetic rats.
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