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

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% sodiumtaurocholate 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. Keywords APD • Severe acute pancreatitis • Apoptosis • PI3K/AKT signaling pathway Abbreviations AKT(PKB) Protein kinase B ANOVA One-way analysis of variance APD Abdominal paracentesis drainage Bcl-2 B-cell lymphoma 2 Caspase3 Cysteine aspartic acid protease 3 ELISA Enzyme-linked immunosorbent assay IL Interleukin MAP Mild acute pancreatitis MODS Multiple organ dysfunction syndrome NF-kB Nuclear factor kappa-light-chain-enhancer of activated B cells PAAF Pancreatitis associated ascitic fluids PI3K Phosphatidylinositide 3-kinases SAP Severe acute pancreatitis SIRS Systemic inflammatory response syndrome TNF-α TNF-α

Protective effects of peptide FK18 against neuro‑excitotoxicity in SH‑SY5Y cells

“…A previous study demonstrated that Akt activity is responsible for as much as 80% of neurotrophin-regulated cell survival, indicating that Akt is the major survival-promoting protein for neurons (38). Akt signaling inhibits apoptosis by regulating the expression of Bcl-2 and Bax and finally, the expression of caspase-3 (39,40). The findings of the present study were consistent with those of the aforementioned studies.…”

The Long-Term DEHP Exposure Confers Multidrug Resistance of Triple-Negative Breast Cancer Cells through ABC Transporters and Intracellular ROS

“…The regulation of PI3K signaling is crucial for maintaining cellular and metabolic function in both cancerous and normal cells. Apart from metabolic processes, several cellular functions, such as cell cycle regulation, cell growth, proliferation, migration, and death (apoptosis) are influenced by PI3K signaling regulation [87][88][89][90]. P13K responds to extracellular stimuli and regulates the intracellular signaling cascade involving Akt, NFκB, p53, and mTOR to achieve its role in cellular functions.…”

Comprehensive Analysis of Differentially Expressed lncRNA, circRNA and mRNA and Their ceRNA Networks in Mice With Severe Acute Pancreatitis

“…It has confirmed that Bmf can function as apoptosis activator ( Hayakawa et al, 2016 ) and Gab1 can plays a central role in cell growth, transformation and apoptosis ( Zhang et al, 2019b ). Reportedly, apoptosis has protective effects on SAP ( Luo et al, 2020 ). Therefore, we speculate that lncRNA AK004187 and lncRNA uc029sug.1 could influence the severity of the disease by regulating the apoptosis of acinar cells in SAP.…”