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腹腔穿刺引流通过抑制HMGB1介导的TLR4信号通路减轻重症急性胰腺炎大鼠的肠道炎症。

Abdominal paracentesis drainage attenuates intestinal inflammation in rats with severe acute pancreatitis by inhibiting the HMGB1-mediated TLR4 signaling pathway.

作者信息

Huang Shang-Qing, Wen Yi, Sun Hong-Yu, Deng Jie, Zhang Yao-Lei, Huang Qi-Lin, Wang Bing, Luo Zhu-Lin, Tang Li-Jun

机构信息

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, Sichuan Province, China.

Basic Medical Laboratory, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China.

出版信息

World J Gastroenterol. 2021 Mar 7;27(9):815-834. doi: 10.3748/wjg.v27.i9.815.

Abstract

BACKGROUND

Our previous studies confirmed that abdominal paracentesis drainage (APD) attenuates intestinal mucosal injury in rats with severe acute pancreatitis (SAP), and improves administration of enteral nutrition in patients with acute pancreatitis (AP). However, the underlying mechanisms of the beneficial effects of APD remain poorly understood.

AIM

To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats, and its potential mechanisms.

METHODS

SAP was induced in male adult Sprague-Dawley rats by 5% sodium taurocholate. Mild AP was induced by intraperitoneal injections of cerulein (20 μg/kg body weight, six consecutive injections). Following SAP induction, a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD. Morphological changes, serum inflammatory mediators, serum and ascites high mobility group box protein 1 (HMGB1), intestinal barrier function indices, apoptosis and associated proteins, and toll-like receptor 4 (TLR4) signaling molecules in intestinal tissue were assessed.

RESULTS

APD significantly alleviated intestinal mucosal injury induced by SAP, as demonstrated by decreased pathological scores, serum levels of D-lactate, diamine oxidase and endotoxin. APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells, and normalized the expression of apoptosis-associated proteins in intestinal tissues. APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1, thus exerting protective effects against SAP-associated intestinal injury.

CONCLUSION

APD improved intestinal barrier function, intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats. The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.

摘要

背景

我们之前的研究证实,腹腔穿刺引流(APD)可减轻重症急性胰腺炎(SAP)大鼠的肠黏膜损伤,并改善急性胰腺炎(AP)患者的肠内营养管理。然而,APD有益作用的潜在机制仍知之甚少。

目的

评估APD对SAP诱导的大鼠肠道炎症及伴随的细胞凋亡的影响及其潜在机制。

方法

用5%牛磺胆酸钠诱导雄性成年Sprague-Dawley大鼠发生SAP。通过腹腔注射雨蛙素(20μg/kg体重,连续注射6次)诱导轻度AP。诱导SAP后,将连接真空球的引流管置于大鼠右下腹以建立APD。评估形态学变化、血清炎症介质、血清和腹水高迁移率族蛋白1(HMGB1)、肠屏障功能指标、细胞凋亡及相关蛋白,以及肠组织中的Toll样受体4(TLR4)信号分子。

结果

APD显著减轻了SAP诱导的肠黏膜损伤,病理评分降低、血清D-乳酸、二胺氧化酶和内毒素水平降低表明了这一点。APD减轻了肠道炎症及伴随的黏膜细胞凋亡,并使肠组织中凋亡相关蛋白的表达正常化。APD显著抑制了由HMGB1介导的肠道TLR4信号通路的激活,从而对SAP相关的肠道损伤发挥保护作用。

结论

APD改善了SAP大鼠的肠屏障功能、肠道炎症反应及伴随的黏膜细胞凋亡。其有益作用可能归因于对HMGB1介导的TLR4信号的抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15df/7941863/a7ebc75c535b/WJG-27-815-g001.jpg

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