Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2021; 27(9): 815-834
Published online Mar 7, 2021. doi: 10.3748/wjg.v27.i9.815
Abdominal paracentesis drainage attenuates intestinal inflammation in rats with severe acute pancreatitis by inhibiting the HMGB1-mediated TLR4 signaling pathway
Shang-Qing Huang, Yi Wen, Hong-Yu Sun, Jie Deng, Yao-Lei Zhang, Qi-Lin Huang, Bing Wang, Zhu-Lin Luo, Li-Jun Tang
Shang-Qing Huang, Yi Wen, Qi-Lin Huang, Bing Wang, Zhu-Lin Luo, Li-Jun Tang, Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
Hong-Yu Sun, Yao-Lei Zhang, Basic Medical Laboratory, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
Jie Deng, Department of Clinical Pharmacy, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
Author contributions: Huang SQ, Wen Y, Sun HY and Deng J contributed equally to this work; Huang SQ and Wen Y participated in the writing of the main manuscript; Tang LJ and Sun HY participated in the study conception and design; Huang SQ, Wen Y, Deng J, Zhang YL and Huang QL participated in the performance of the experiments; Deng J, Zhang YL and Huang QL participated in statistical data analysis, and interpretation; Deng J, Wang B and Luo ZL participated in preparing all the figures; Tang LJ and Sun HY participated in the revision of the manuscript and final approval.
Supported by The National Natural Science Foundation of China, No. 81772001; the National Clinical Key Subject of China, No. 41732113; and the Technology Plan Program of Sichuan Province, No. 2019JY0277 and No. 2020YFSY0022.
Institutional review board statement: The experimental procedures were reviewed and approved by the Institutional Ethics Committee (No. A20180252004) at the General Hospital of Western Theater Command (Chengdu, China).
Institutional animal care and use committee statement: The experimental procedures were reviewed and approved by the Institutional Animal Care and Use Committee at the General Hospital of Western Theater Command (Chengdu, China), and were conducted in accordance with the established International Guiding Principles for Animal Research.
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.
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: Li-Jun Tang, MD, PhD, Chief Doctor, Professor, Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), No. 270 Rongdu Road, Jinniu District, Chengdu 610083, Sichuan Province, China. tanglj2016@163.com
Received: November 7, 2020
Peer-review started: November 7, 2020
First decision: December 3, 2020
Revised: December 14, 2020
Accepted: February 1, 2021
Article in press: February 1, 2021
Published online: March 7, 2021
Processing time: 116 Days and 6.4 Hours
Abstract
BACKGROUND

Our previous studies confirmed that abdominal paracentesis drainage (APD) attenuates intestinal mucosal injury in rats with severe acute pancreatitis (SAP), and improves administration of enteral nutrition in patients with acute pancreatitis (AP). However, the underlying mechanisms of the beneficial effects of APD remain poorly understood.

AIM

To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats, and its potential mechanisms.

METHODS

SAP was induced in male adult Sprague-Dawley rats by 5% sodium taurocholate. Mild AP was induced by intraperitoneal injections of cerulein (20 μg/kg body weight, six consecutive injections). Following SAP induction, a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD. Morphological changes, serum inflammatory mediators, serum and ascites high mobility group box protein 1 (HMGB1), intestinal barrier function indices, apoptosis and associated proteins, and toll-like receptor 4 (TLR4) signaling molecules in intestinal tissue were assessed.

RESULTS

APD significantly alleviated intestinal mucosal injury induced by SAP, as demonstrated by decreased pathological scores, serum levels of D-lactate, diamine oxidase and endotoxin. APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells, and normalized the expression of apoptosis-associated proteins in intestinal tissues. APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1, thus exerting protective effects against SAP-associated intestinal injury.

CONCLUSION

APD improved intestinal barrier function, intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats. The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.

Keywords: Abdominal paracentesis drainage; Severe acute pancreatitis; High mobility group box 1; Toll-like receptor 4; Nuclear factor-κB

Core Tip: We provide the first evidence that abdominal paracentesis drainage (APD) plays a protective role in intestinal inflammation and accompanying apoptosis induced by severe acute pancreatitis (SAP). Our key findings were: (1) APD decreased serum levels of indices related to intestinal injury and improved intestinal barrier function; (2) APD alleviated intestinal inflammation and accompanying mucosal cell apoptosis; and (3) The beneficial effects of APD in ameliorating intestinal injury were due to suppressed activation of intestinal toll-like receptor 4/nuclear factor-κB signaling pathway mediated by high mobility group box protein 1. We elucidated the molecular mechanism underlying APD treatment of SAP and its complications.