Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2020; 26(1): 35-54
Published online Jan 7, 2020. doi: 10.3748/wjg.v26.i1.35
Abdominal paracentesis drainage ameliorates myocardial injury in severe experimental pancreatitis rats through suppressing oxidative stress
Yi Wen, Hong-Yu Sun, Zhen Tan, Ruo-Hong Liu, Shang-Qing Huang, Guang-Yu Chen, Hao Qi, Li-Jun Tang
Yi Wen, Hong-Yu Sun, Zhen Tan, Ruo-Hong Liu, Shang-Qing Huang, Guang-Yu Chen, Li-Jun Tang, Department of General Surgery and 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
Hao Qi, Department of Dermatology, The Air Force Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
Author contributions: Wen Y, Sun HY and Tan Z contributed equally to this work; Tang LJ designed the experiments; Wen Y, Tan Z, Liu RH and Huang SQ performed the experiments; Wen Y, Sun HY and Tan Z analyzed the data; Chen GY and Hao Q prepared and finished all the figures; Wen Y and Tan Z drafted the manuscript; Tang LJ and Sun HY refined and edited the manuscript; Tang LJ supervised the study.
Supported by National Natural Science Foundation of China, No. 81772001; National Clinical Key Subject of China, No. 41792113; and Technology Plan Program of Sichuan Provence, No. 2015SZ0229, No. 2016HH0067, No. 2018JY0041 and No. 2019YJ0277.
Institutional review board statement: This study was approved by the Institutional Review Board of Chengdu Military General Hospital.
Institutional animal care and use committee statement: All animal protocols were approved by Animal Welfare law of Chengdu Military General Hospital, Chengdu, China, No. A20170312004.
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: In the manuscript, the ARRIVE Guidelines have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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, Chief of Surgery, Department of General Surgery and Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command, No. 270 Rongdu Road, Jinniu District, Chengdu 610083, Sichuan Province, China. tanglj2016@163.com
Received: September 26, 2019
Peer-review started: September 26, 2019
First decision: November 4, 2019
Revised: December 6, 2019
Accepted: December 13, 2019
Article in press: December 13, 2019
Published online: January 7, 2020
Processing time: 103 Days and 4.5 Hours
ARTICLE HIGHLIGHTS
Research background

Severe acute pancreatitis (SAP) is a fatal systemic disease usually complicated with multiple distant organ injury. Among the distant organ injury, SAP-associated cardiac injury (SACI) occurs in a variable proportion of patients, and cardiac decompensation even causes death. Despite constant understanding in the pathogenesis of SAP and significant improvement in clinical management, the mortality rate remains high and unacceptable. In our previous study, early abdominal paracentesis drainage (APD) was found to effectively relieve or control the severity of SAP and maintenance of organ function through removing pancreatitis associated ascitic fluids (PAAF). However, the effect of APD treatment on SAP-associated cardiac injury and the possible mechanism are yet to be elucidated.

Research motivation

Inflammatory mediators exert a vital role in the initiation and progression of SAP in the early stage. High concentration of high mobility group box 1 (HMGB1) in the pancreatitis associated ascitic fluids has been confirmed. Thus, we want to further study whether HMGB1 in ascites is related to SAP-associated cardiac injury, which may be a novel mechanism behind the effectiveness of APD on SAP.

Research objectives

The aim of this study was to determine the protective effects of APD treatment on SAP-associated cardiac injury and explore the potential mechanism.

Research methods

In the present study, SAP was induced by 5% sodium taurocholate retrograde injection in Sprague-Dawley rats. Mild acute pancreatitis was induced by six consecutively intraperitoneal injections of cerulein (20 μg/kg rat weight). APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after SAP induction. Morphological staining, serum amylase and inflammatory mediators, serum and ascites HMGB1, cardiac-related enzymes indexes and cardiac function and oxidative stress markers were performed. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) mRNA was identified by real-time polymerase chain reaction. Apoptosis-associated proteins and protein expression of NOX were measured by western blot.

Research results

APD notably improved pancreatic and cardiac morphological changes, attenuated the alterations in serum amylase, inflammatory mediators, cardiac enzymes and function, reactive oxygen species production and oxidative markers, alleviated myocardial cell apoptosis, reversed the expression of apoptosis-associated proteins, downregulated HMGB1 level in serum and inhibited NOX hyperactivity. Furthermore, the activation of cardiac NOX by pancreatitis associated ascitic fluids intraperitoneal injection was effectively inhibited by adding anti-HMGB1 neutralizing antibody in rats with mild acute pancreatitis.

Research conclusions

APD treatment could exert cardioprotective effects on SAP-associated cardiac injury through suppressing HMGB1-mediated oxidative stress.

Research perspectives

Our study provided new evidence of the efficacy and safety of APD treatment on SAP and revealed a novel mechanism behind the effectiveness of APD on SAP. However, in this study we still do not know how HMGB1 modulates NOX under SAP conditions. In the next experiments, we should detect the expression profile of HMGB1 receptor protein in the heart and utilize a special receptor protein knockout model to clarify the precise mechanisms.