Published online Jan 7, 2020. doi: 10.3748/wjg.v26.i1.35
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
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.
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.
The aim of this study was to determine the protective effects of APD treatment on SAP-associated cardiac injury and explore the potential mechanism.
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.
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.
APD treatment could exert cardioprotective effects on SAP-associated cardiac injury through suppressing HMGB1-mediated oxidative stress.
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.