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
Abstract
BACKGROUND

The mechanisms underlying gastrointestinal (GI) dysmotility with ulcerative colitis (UC) have not been fully elucidated. The enteric nervous system (ENS) plays an essential role in the GI motility. As a vital neurotransmitter in the ENS, the gas neurotransmitter nitric oxide (NO) may impact the colonic motility. In this study, dextran sulfate sodium (DSS)-induced UC rat model was used for investigating the effects of NO by examining the effects of rate-limiting enzyme nitric oxide synthase (NOS) changes on the colonic motility as well as the role of the ENS in the colonic motility during UC.

AIM

To reveal the relationship between the effects of NOS expression changes in NOS-containing nitrergic neurons and the colonic motility in a rat UC model.

METHODS

Male rats (n = 8/each group) were randomly divided into a control (CG), a UC group (EG1), a UC + thrombin derived polypeptide 508 trifluoroacetic acid (TP508TFA; an NOS agonist) group (EG2), and a UC + NG-monomethyl-L-arginine monoacetate (L-NMMA; an NOS inhibitor) group (EG3). UC was induced by administering 5.5% DSS in drinking water without any other treatment (EG1), while the EG2 and EG3 were gavaged with TP508 TFA and L-NMMA, respectively. The disease activity index (DAI) and histological assessment were recorded for each group, whereas the changes in the proportion of colonic nitrergic neurons were counted using immunofluorescence histochemical staining, Western blot, and enzyme linked immunosorbent assay, respectively. In addition, the contractile tension changes in the circular and longitudinal muscles of the rat colon were investigated in vitro using an organ bath system.

RESULTS

The proportion of NOS-positive neurons within the colonic myenteric plexus (MP), the relative expression of NOS, and the NOS concentration in serum and colonic tissues were significantly elevated in EG1, EG2, and EG3 compared with CG rats. In UC rats, stimulation with agonists and inhibitors led to variable degrees of increase or decrease for each indicator in the EG2 and EG3. When the rats in EGs developed UC, the mean contraction tension of the colonic smooth muscle detected in vitro was higher in the EG1, EG2, and EG3 than in the CG group. Compared with the EG1, the contraction amplitude and mean contraction tension of the circular and longitudinal muscles of the colon in the EG2 and EG3 were enhanced and attenuated, respectively. Thus, during UC, regulation of the expression of NOS within the MP improved the intestinal motility, thereby favoring the recovery of intestinal functions.

CONCLUSION

In UC rats, an increased number of nitrergic neurons in the colonic MP leads to the attenuation of colonic motor function. To intervene NOS activity might modulate the function of nitrergic neurons in the colonic MP and prevent colonic motor dysfunction. These results might provide clues for a novel approach to alleviate diarrhea symptoms of UC patients.

Keywords: Nitrergic neurons; Nitric oxide; Nitric oxide synthase; Ulcerative colitis; Colonic motility; Colonic myenteric plexus

Core Tip: This study focused on the effects of nitrergic neurons in the myenteric plexus (MP) on colonic motor function in rats with ulcerative colitis (UC). The results suggest that an increased number of nitrergic neurons in the colonic MP of the UC rats leads to reduced colon contractile function. Therefore, the regulation of the activity of nitrergic neurons in the colonic MP through interference with the activities of nitric oxide synthase might be a novel potential and prospective way to reduce the diarrhea symptoms in UC patients.