Department of Hepatobiliary Surgery, the Affiliated Hospital of Southwestern Medical University, Luzhou, 646000, Sichuan, China.
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.
Apoptosis. 2020 Apr;25(3-4):290-303. doi: 10.1007/s10495-020-01597-2.
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.
我们之前的研究表明,腹腔穿刺引流(APD)是治疗重症急性胰腺炎(SAP)患者的一种安全有效的策略。然而,APD 治疗背后的潜在机制仍知之甚少。鉴于细胞凋亡是 SAP 的一种关键病理反应,我们旨在研究 APD 对 SAP 期间胰腺组织细胞凋亡的影响,并探讨其潜在的分子机制。通过逆行 5%牛磺胆酸钠诱导 SAP,APD 组在 SAP 诱导后立即在大鼠右下腹部插入引流管。测量组织病理学染色、血清淀粉酶、内毒素和炎症介质。还评估了细胞凋亡、凋亡相关蛋白和信号通路。我们的结果表明,APD 治疗可显著减轻 SAP 大鼠的胰腺损伤,降低血清淀粉酶、内毒素、TNF-α、IL-1 和 IL-6 水平。值得注意的是,APD 治疗增强了胰腺组织中的细胞凋亡并减少了坏死,这可以通过隧道染色、促凋亡蛋白(Cleaved-caspase-3 和 bax)的增加和抗凋亡蛋白(Bcl-2)的减少来证明。此外,PI3K/AKT 和 NF-kB 信号通路的调节途径进一步证实了 APD 对细胞凋亡的影响。这些结果表明,APD 通过抑制 PI3K/AKT 信号通路增强细胞凋亡来减轻 SAP 的严重程度。我们的研究结果为理解 APD 在 SAP 患者中的有效性提供了新的见解。