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
ARTICLE HIGHLIGHTS
Research background

Severe acute pancreatitis (SAP) is an abdominal disease characterized by extensive inflammation and tissue necrosis of the pancreas and usually accompanied by multiple organ damage, resulting in high mortality. Intestinal injury is the most common extrapancreatic complication and is closely related to the severity of SAP. Our previous studies proved that elimination of pancreatitis associated ascitic fluids (PAAF) through early abdominal paracentesis drainage (APD) attenuates intestinal mucosal injury and protects intestinal barrier effectively, but the potential molecular mechanisms responsible for the beneficial effect are yet to be clarified.

Research motivation

The inflammatory response plays an essential role in the pathological process of SAP-induced intestinal injury. High concentration of high mobility group box protein 1 (HMGB1) participates in remote organ damage and has been confirmed during SAP. Based on our previous research, we further investigate whether HMGB1 in ascites is related to intestinal inflammation and apoptosis under SAP conditions, which may reveal the underlying mechanism of APD in SAP.

Research objectives

The purpose of the present experiment was to explore the effect of APD treatment on intestinal inflammation and apoptosis induced by SAP in rats, and its potential mechanisms.

Research methods

SAP was induced in male adult Sprague-Dawley rats by 5% sodium taurocholate. Mild acute pancreatitis 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 for APD. Morphological staining, serum amylase, lipase and inflammatory mediators, serum and ascites HMGB1, serum indices which reflect intestinal barrier function, apoptosis and associated proteins in intestinal tissue were assessed. The expression levels of key proteins in the toll-like receptor 4 (TLR4) signaling pathway were also examined.

Research results

The results demonstrated that APD notably alleviated the changes in pancrease and intestinal mucosa, attenuated the alterations in serum amylase, lipase and inflammatory mediators, improved intestinal barrier function, lessened intestinal inflammation and accompanying apoptosis of mucosal cells, and reversed the expression of apoptosis-associated proteins. APD significantly inhibited activation of the intestinal TLR4 signaling pathway mediated by HMGB1 in intestinal tissue, and thus plays a protective role in SAP-associated intestinal injury.

Research conclusions

APD treatment effectively improved intestinal barrier function, ameliorated the intestinal inflammatory response and mucosa cell apoptosis in rats with SAP. The protective effects are potentially due to the inhibition of the HMGB1-mediated TLR4 signaling pathway.

Research perspectives

The present study provided new evidence of the efficacy and safety of APD treatment on SAP, and provided a novel molecular mechanism associated with the effect of APD on SAP-induced intestinal injury. However, in this research we did not detect the expression change of HMGB1 in intestinal tissue. In our next experiments, we will attempt to verify the relationship between intestinal HMGB1 and PAAF to further reveal the precise mechanisms of APD treatment in SAP.