Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2020; 26(33): 4945-4959
Published online Sep 7, 2020. doi: 10.3748/wjg.v26.i33.4945
Resveratrol alleviates intestinal mucosal barrier dysfunction in dextran sulfate sodium-induced colitis mice by enhancing autophagy
Hang-Hai Pan, Xin-Xin Zhou, Ying-Yu Ma, Wen-Sheng Pan, Fei Zhao, Mo-Sang Yu, Jing-Quan Liu
Hang-Hai Pan, Wen-Sheng Pan, Fei Zhao, Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Xin-Xin Zhou, Mo-Sang Yu, Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Ying-Yu Ma, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Jing-Quan Liu, Critical Care Unit, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Author contributions: Pan HH designed the experiments; Ma YY, Yu MS and Zhao F performed the experiments and analyzed the data; Pan HH and Zhou XX drafted the manuscript; Ma YY critically revised the manuscript; Liu JQ and Pan WS offered help during the experiments; all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81600414; Medical Health Science and Technology Project of Zhejiang Provincial Health Commission, No. 2018255969; Zhejiang TCM Science and Technology Project, No. 2016ZA123 and No. 2018ZA013.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of Zhejiang Chinese Medical University.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethics Committee of Zhejiang Chinese Medical University.
Conflict-of-interest statement: No potential conflicts of interest exist.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ying-Yu Ma, MD, Research Assistant, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou 310014, Zhejiang Province, China. myy011525@163.com
Received: May 17, 2020
Peer-review started: May 17, 2020
First decision: June 18, 2020
Revised: June 27, 2020
Accepted: August 12, 2020
Article in press: August 12, 2020
Published online: September 7, 2020
Abstract
BACKGROUND

Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis (UC). Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice. Resveratrol exerts anti-inflammatory functions by regulating autophagy.

AIM

To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium (DSS)-induced ulcerative colitis mice.

METHODS

Male C57BL/6 mice were divided into four groups: negative control group, DSS model group, DSS + resveratrol group, and DSS + 5-aminosalicylic acid group. The severity of colitis was assessed by the disease activity index, serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay. Colon tissues were stained with haematoxylin and eosin, and mucosal damage was evaluated by mean histological score. The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis. In addition, the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot, and morphology of autophagy was observed by transmission electron microscopy.

RESULTS

The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42, 3.81, and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α, interleukin-6 and interleukin-1β, respectively, in DSS-induced colitis mice compared with DSS group (P < 0.05). The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased, and were increased in resveratrol-treated colitis group. Resveratrol also increased the levels of LC3B (by 1.39-fold compared with DSS group) and Beclin-1 (by 1.49-fold compared with DSS group) (P < 0.05), as well as the number of autophagosomes, which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy.

CONCLUSION

Resveratrol treatment decreased the expression of inflammatory factors, increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction; this effect may be achieved by enhancing autophagy in intestinal epithelial cells.

Keywords: Resveratrol, Ulcerative colitis, Autophagy, Intestinal mucosal barrier;Dextran sulfate sodium-induced colitis, Intestinal inflammation

Core tip: We established a chronic colitis model successfully via administration of dextran sulfate sodium (DSS), and we found that resveratrol ameliorates the production of the inflammatory cytokines in DSS-induced colitis mice. Meanwhile, resveratrol treatment alleviated intestinal mucosal barrier dysfunction in DSS-induced colitis and increased the expression of the tight junction proteins occludin and ZO-1. Further studies showed that resveratrol treatment increased the levels of LC3B and Beclin-1 in the colons of colitis mice, as well as the number of autophagosomes, which may via enhancing autophagy.