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姜黄素可预防肠道缺血再灌注损伤:紧密连接蛋白ZO-1及肿瘤坏死因子-α相关机制的参与

Curcumin protects against the intestinal ischemia-reperfusion injury: involvement of the tight junction protein ZO-1 and TNF-α related mechanism.

作者信息

Tian Shuying, Guo Ruixue, Wei Sichen, Kong Yu, Wei Xinliang, Wang Weiwei, Shi Xiaomeng, Jiang Hongyu

机构信息

Department of Gastroenterology, Cangzhou Central Hospital, Hebei 061001, China.

出版信息

Korean J Physiol Pharmacol. 2016 Mar;20(2):147-52. doi: 10.4196/kjpp.2016.20.2.147. Epub 2016 Feb 23.

Abstract

Present study aimed to investigate the eff ect of curcumin-pretreatment on intestinal I/R injury and on intestinal mucosa barrier. Thirty Wistar rats were randomly divided into: sham, I/R, and curcumin groups (n=10). Animals in curcumin group were pretreated with curcumin by gastric gavage (200 mg/kg) for 2 days before I/R. Small intestine tissues were prepared for Haematoxylin & Eosin (H&E) staining. Serum diamine oxidase (DAO) and tumor necrosis factor (TNF)-α levels were measured. Expression of intestinal TNF-α and tight junction protein (ZO-1) proteins was detected by Western blot and/or immunohistochemistry. Serum DAO level and serum and intestinal TNF-α leves were signifi cantly increased after I/R, and the values were markedly reduced by curcumin pretreatment although still higher than that of sham group (p<0.05 or p<0.001). H&E staining showed the significant injury to intestinal mucosa following I/R, and curcumin pretreatment signifi cantly improved the histological structure of intestinal mucosa. I/R insult also induced significantly down-regulated expression of ZO-1, and the eff ect was dramatically attenuated by curcumin-pretreatment. Curcumin may protect the intestine from I/R injury through restoration of the epithelial structure, promotion of the recovery of intestinal permeability, as well as enhancement of ZO-1 protein expression, and this eff ect may be partly attributed to the TNF-α related pathway.

摘要

本研究旨在探讨姜黄素预处理对肠缺血/再灌注损伤及肠黏膜屏障的影响。30只Wistar大鼠随机分为:假手术组、缺血/再灌注组和姜黄素组(n = 10)。姜黄素组动物在缺血/再灌注前2天通过胃管灌胃给予姜黄素(200 mg/kg)。制备小肠组织进行苏木精-伊红(H&E)染色。检测血清二胺氧化酶(DAO)和肿瘤坏死因子(TNF)-α水平。通过蛋白质印迹法和/或免疫组织化学检测肠组织中TNF-α和紧密连接蛋白(ZO-1)的表达。缺血/再灌注后血清DAO水平以及血清和肠组织中TNF-α水平显著升高,姜黄素预处理可使这些值明显降低,尽管仍高于假手术组(p < 0.05或p < 0.001)。H&E染色显示缺血/再灌注后肠黏膜有明显损伤,姜黄素预处理显著改善了肠黏膜的组织结构。缺血/再灌注损伤还导致ZO-1表达显著下调,姜黄素预处理可显著减轻这种作用。姜黄素可能通过恢复上皮结构、促进肠通透性恢复以及增强ZO-1蛋白表达来保护肠道免受缺血/再灌注损伤,这种作用可能部分归因于TNF-α相关途径。

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