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

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          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.

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          Most cited references35

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          Acute Pancreatitis.

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            Bcl-2 and Bcl-xL play important roles in the crosstalk between autophagy and apoptosis.

            Autophagy and apoptosis play important roles in the development, cellular homeostasis and, especially, oncogenesis of mammals. They may be triggered by common upstream signals, resulting in combined autophagy and apoptosis. In other instances, they may be mutually exclusive. Recent studies have suggested possible molecular mechanisms for crosstalk between autophagy and apoptosis. Bcl-2 and Bcl-xL, the well-characterized apoptosis guards, appear to be important factors in autophagy, inhibiting Beclin 1-mediated autophagy by binding to Beclin 1. In addition, Beclin 1, Bcl-2 and Bcl-xL can cooperate with Atg5 or Ca(2+) to regulate both autophagy and apoptosis. Thus, Bcl-2 and Bcl-xL represent a molecular link between autophagy and apoptosis. Here, we discuss the possible roles of Bcl-2 and Bcl-xL in apoptosis and autophagy, and the crosstalk between them. © 2010 The Authors Journal compilation © 2010 FEBS.
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              A better model of acute pancreatitis for evaluating therapy.

              Existing models of acute pancreatitis have limitations to studying novel therapy. Whereas some produce mild self-limited pancreatitis, others result in sudden necrotizing injury. The authors developed an improved model providing homogeneous moderately severe injury by superimposing secretory hyperstimulation on minimal intraductal bile acid exposure. Sprague-Dawley rats (n = 231) received low-pressure intraductal glycodeoxycholic acid (GDOC) at very low (5 or 10 mmol/L) concentrations followed by intravenous cerulein. Cerulein or GDOC alone caused only very mild inflammation. However, GDOC combined with cerulein was uniformly associated with more edema (p less than 0.0005), acinar necrosis (p less than 0.01), inflammation (p less than 0.006), and hemorrhage (p less than 0.01). Pancreatic injury was further increased and death was potentiated by increasing volume and duration of intraductal low-dose GDOC infusion. There was significant morphologic progression between 6 and 24 hours. The authors conclude that (1) combining minimal intraductal bile acid exposure with intravenous hyperstimulation produces homogeneous pancreatitis of intermediate severity that can be modulated at will; (2) the injury is progressive over at least 24 hours with finite mortality rate; (3) the model provides superior opportunity to study innovative therapy.
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                Author and article information

                Contributors
                tanglj2016@163.com
                shongyu2008@163.com
                Journal
                Apoptosis
                Apoptosis
                Apoptosis
                Springer US (New York )
                1360-8185
                1573-675X
                25 February 2020
                25 February 2020
                2020
                : 25
                : 3
                : 290-303
                Affiliations
                [1 ]Department of Hepatobiliary Surgery, the Affiliated Hospital of Southwestern Medical University, Luzhou, 646000 Sichuan China
                [2 ]GRID grid.413855.e, ISNI 0000 0004 1764 5163, 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 China
                Author information
                http://orcid.org/0000-0001-6000-9515
                Article
                1597
                10.1007/s10495-020-01597-2
                7181427
                32100210
                3969f4fd-953e-4dcd-b29d-f5b67ea702fa
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Funding
                Funded by: The National Natural Science Foundation of China
                Award ID: NO. 81772001
                Award Recipient :
                Funded by: The National Clinical Key Subject of China
                Award ID: NO. 41792113
                Award Recipient :
                Funded by: The Technology Plan Program of Sichuan Provence
                Award ID: NO. 2015SZ0229
                Award ID: NO.2019YJ0277
                Award ID: NO.2018JY0041
                Award Recipient :
                Categories
                Article
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2020

                Molecular biology
                apd,severe acute pancreatitis,apoptosis,pi3k/akt signaling pathway
                Molecular biology
                apd, severe acute pancreatitis, apoptosis, pi3k/akt signaling pathway

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