Basic Study
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World J Gastroenterol. Aug 7, 2022; 28(29): 3854-3868
Published online Aug 7, 2022. doi: 10.3748/wjg.v28.i29.3854
Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis
Yan-Rong Li, Yan Li, Yuan Jin, Mang Xu, Hong-Wei Fan, Qian Zhang, Guo-He Tan, Jing Chen, Yun-Qing Li
Yan-Rong Li, Yun-Qing Li, Department of Human Anatomy, Basic Medical College, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
Yan-Rong Li, Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, Liaoning Province, China
Yan Li, Yuan Jin, Qian Zhang, Yun-Qing Li, Department of Human Anatomy, Basic Medical College, Zunyi Medical University, Zunyi 563006, Guizhou Province, China
Mang Xu, Department of Anatomy, Basic Medical College, Dali University, Dali 671000, Yunnan Province, China
Hong-Wei Fan, Department of Anatomy, Histology and Embryology, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
Guo-He Tan, Key Lab of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
Guo-He Tan, School of Basic Medical Sciences and Center for Translational Medicine, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
Jing Chen, Yun-Qing Li, Department of Anatomy, Histology and Embryology and K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
Yun-Qing Li, Department of Human Anatomy, College of Preclinical Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
Yun-Qing Li, Key Laboratory of Brain Science Research and Transformation in Tropical Environment of Hainan Province, Hainan Medical University, Haikou 571199, Hainan Province, China
Author contributions: Li YQ and Chen J designed the study and edited the manuscript; Li YR, Li Y, Xu M, Jin Y, and Fan HW conducted the experiments; Li YR and Li Y completed the data analysis; Zhang Q and Tan GH provided language modification; Li YR and Li Y wrote the manuscript; all authors read and approved the final manuscript; and Li YR and Li Y contributed equally in carrying out this study and writing the manuscript.
Supported by National Natural Science Foundation of China, No. 31971112; Natural Science Foundation of Liaoning Province, No. 2021-MS-330; and Innovation Capability Support Program of Shaanxi, No. 2021TD-57.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (licence No. SCXK (Shan) 2019-001, Animal Experiment Center, The Fourth Military Medical University, China; protocol No. IACUC-20211101, The Laboratory Animal Welfare and Ethics Committee at The Fourth Military Medical University, China).
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yun-Qing Li, PhD, Professor, Department of Human Anatomy, Basic Medical College, Guangxi Medical University, No. 22 Shuang-Yong Road, Nanning 530000, Guangxi Zhuang Autonomous Region, China. deptanat@fmmu.edu.cn
Received: December 16, 2021
Peer-review started: December 16, 2021
First decision: April 16, 2022
Revised: April 27, 2022
Accepted: July 6, 2022
Article in press: July 6, 2022
Published online: August 7, 2022
Processing time: 229 Days and 18.6 Hours
ARTICLE HIGHLIGHTS
Research background

Ulcerative colitis (UC) is a nonspecific inflammatory intestinal disorder with a complex etiology and poorly understood pathogenesis. The association between abnormal intestinal motility and UC has gained increasing attention over the past years. The enteric nervous system (ENS) regulates gut motility and based on their functions, has been divided into inhibitory and excitatory neurons, which mainly regulate the gut motility in terms of relaxation and contraction via different neurotransmitters. Nitrergic neurons are typical inhibitory neurons in the ENS and act through the neurotransmitter nitric oxide, which is synthetized by the rate-limiting enzyme nitric oxide synthase (NOS), whose expression changes might affect the motor function of the gut.

Research motivation

UC is an intestinal disease with abdominal pain and diarrhea as the main symptoms, which are associated with abnormal gastrointestinal motility. Alterations in the amount of enteric neurotransmitters may change the number of enteric neurons. Nitrergic neurons are well-established enteric inhibitory neurons, and modification of its expression may interfere with its regulatory effect on intestinal motility and improve the symptoms of abdominal pain and diarrhea in UC.

Research objectives

This study aimed to investigate the relationship between colonic NOS expression changes and colonic motility in dextran sulfate sodium (DSS)-induced UC rats, and to explore the effects of nitrergic neurons on colonic motility in UC rats to discover the potential mechanisms for the treatment of UC.

Research methods

UC was induced in adult male rats with 5.5% DSS, and part of them were administered with NOS agonists and inhibitors. The rats were divided into control (CG), UC (EG1), UC + agonist (EG2), and UC + inhibitor (EG3) groups. The changes in tissue expression, relative protein expression, and concentration of NOS in rats were detected by immunofluorescence histochemical double staining, Western blot, and ELISA techniques, respectively. The effect of nitrergic neurons on colonic motility was examined by the changes in colonic circular muscle (CM) and longitudinal muscle (LM) contraction tension in vitro.

Research results

Compared with CG rats, the proportion of NOS positive neurons within the colonic myenteric plexus (MP), the relative expression of NOS, and the concentration of NOS in both serum and colonic tissue were significantly higher in EG rats. After administration of NOS agonists and inhibitors, various degrees of increase and decrease were observed in EG2 and EG3 rats, respectively. The contraction amplitude and mean contraction tension of the CM and LM in rat colon after administration of agonists and inhibitors were attenuated and enhanced in vitro, respectively. For UC, regulating the expression of NOS within the MP may improve intestinal motility, thereby favoring the recovery of intestinal function.

Research conclusions

Nitrergic neurons within the rat colonic MP are involved in the regulation of colonic motility. Increased NOS in the colonic MP of UC rats causes nitrergic neurons amplification, leading to decreased colonic contraction function. Modulation of NOS levels within colonic MP can alter nitrergic neuron expression and adjust the motor activity of the intestinal smooth muscle, which can further improve colonic motor function, moderate UC symptoms, and provide evidence for the development of new drugs against UC.

Research perspectives

This study demonstrated increased NOS expression in the colonic MP of UC rats, with a possible corresponding increase in nitrergic neuron expression and a decrease in colonic contraction function in UC rats. Thus, by regulating the expression of NOS in the colonic MP, colonic motor function and interruption in the pathogenesis of UC can be achieved, thus providing a novel insight into the treatment of UC.