Aspirin Protects against Acinar Cells Necrosis in Severe Acute Pancreatitis in Mice.

Guotao Lu,George Liu,Yanbing Ding,Yuhui Wang,Yiyuan Pan,Jianfeng Tu,Zhihui Tong,Lin Gao,Weiqin Li,Jinjiao Liu

doi:10.1155/2016/6089430

Abstract

Aspirin has a clear anti-inflammatory effect and is used as an anti-inflammatory agent for both acute and long-term inflammation. Previous study has indicated that aspirin alleviated acute pancreatitis induced by caerulein in rat. However, the role of aspirin on severe acute pancreatitis (SAP) and the necrosis of pancreatic acinar cell are not yet clear. The aim of this study was to determine the effects of aspirin treatment on a SAP model induced by caerulein combined with Lipopolysaccharide. We found that aspirin reduced serum amylase and lipase levels, decreased the MPO activity, and alleviated the histopathological manifestations of pancreas and pancreatitis-associated lung injury. Proinflammatory cytokines were decreased and the expression of NF-κB p65 in acinar cell nuclei was suppressed after aspirin treatment. Furthermore, aspirin induced the apoptosis of acinar cells by TUNEL assay, and the expression of Bax and caspase 3 was increased and the expression of Bcl-2 was decreased. Intriguingly, the downregulation of critical necrosis associated proteins RIP1, RIP3, and p-MLKL was observed; what is more, we additionally found that aspirin reduced the COX level of pancreatic tissue. In conclusion, our data showed that aspirin could protect pancreatic acinar cell against necrosis and reduce the severity of SAP. Clinically, aspirin may potentially be a therapeutic intervention for SAP.

Highlights

Acute pancreatitis (AP) is a complex pathological process, depending on autodigestion caused by premature activation of zymogens
We for the first time confirmed that aspirin could remarkably alleviate the severity of severe acute pancreatitis (SAP) and protects against acinar cells necrosis by downregulation of RIP1, RIP3, and p-MLKL expressions
We investigated the effect of aspirin in a model of SAP and associated lung injury in mice

Summary

Introduction

Acute pancreatitis (AP) is a complex pathological process, depending on autodigestion caused by premature activation of zymogens. Numerous studies showed that pancreatic necrosis is crucial for the development of mild acute pancreatitis (MAP) to severe acute pancreatitis (SAP) [4,5,6]. MAP has a short course, and the pancreatic structure and function could be fully restored, while, in SAP, once the acinar cells necrosis happened, the rupture of acinar cell membrane could release a series of inflammatory factors, including. A large number of clinical and experimental researches suggest that, after AP, especially after SAP, endocrine and exocrine function of the pancreas often suffer varying degrees of damage, even developing permanent sequelae of pancreatic dysfunction [7,8,9].

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