Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

Chen Luo,Bing Wang,Lijun Tang,Zhu Huang,Hongyu Sun,Xiaohui Yuan,Qilin Huang,Yi Yang

doi:10.1007/s10495-020-01597-2

Abstract

Our previous studies have shown that abdominal paracentesis drainage (APD) is a safe and effective strategy for patients with severe acute pancreatitis (SAP). However, the underlying mechanisms behind APD treatment remain poorly understood. Given that apoptosis is a critical pathological response of SAP, we here aim to investigate the effect of APD on cell apoptosis in pancreatic tissues during SAP and to explore its potential molecular mechanism. SAP was induced by 5% sodium-taurocholate retrograde while APD group was inserted a drainage tube into the right lower abdomen of rats immediately after SAP induction. Histopathological staining, serum amylase, endotoxin and inflammatory mediators were measured. Cell apoptosis, apoptosis-related proteins and signaling pathway were also evaluated. Our results demonstrated that APD treatment significantly attenuated pancreatic damage and decreased the serum levels of amylase, endotoxin, TNF-α, IL-1 and IL-6 in rats with SAP. Notably, APD treatment enhanced cell apoptosis and reduced necrosis in pancreatic tissues, as evidenced by Tunnel staining, the increased pro-apoptosis proteins (Cleaved-caspase-3 and bax) and decreased anti-apoptosis protein (Bcl-2). Moreover, the effect of APD on cell apoptosis was further confirmed by the regulatory pathway of PI3K/AKT and NF-kB signaling pathway. These results suggest that APD attenuates the severity of SAP by enhancing cell apoptosis via suppressing PI3K/AKT signaling pathway. Our findings provide new insights for understanding the effectiveness of APD in patients with SAP.

Highlights

Severe acute pancreatitis (SAP) is a fatal clinical condition usually complicated with systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS)
We systematically investigated the influence of abdominal paracentesis drainage (APD) treatment on apoptosis in rats with SAP and determined whether Phosphoinositide 3-kinase (PI3K)/AKT signaling play a crucial role during this treatment process
The expression of NF-kB65, a known downstream signaling molecule, was found to have a significant decrease in APD group than that in SAP at various time points (Fig. 4b, f). These results demonstrate that APD treatment by removing Pancreatic associated ascites fluid (PAAF) significantly suppressed PI3K/AKT signaling pathway in SAP rats, suggesting that PI3K/AKT signaling may be responsible for the protective effects of APD on pancreatic injury induced by SAP

Summary

Introduction

Severe acute pancreatitis (SAP) is a fatal clinical condition usually complicated with systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS). The mortality rate of SAP is still up to 20–30% [1]. The key issue is that there is no effective therapy to control the progression of SAP. Pancreatic associated ascites fluid (PAAF) is known to play a critical role in the pathogenesis of SAP because it contains various. Our previous clinical and experimental studies showed that abdominal paracentesis drainage (APD) attenuated the outcomes of SAP safely and effectively through removing PAAF [6,7,8,9,10]. Little is known about the underlying mechanisms responsible for APD treatment for SAP

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Conclusion