大黄素对肠黏膜屏障损伤的保护作用及机制研究

Protective effects of emodin on intestinal mucosal barrier injury

目的观察大黄素对大鼠肠缺血再灌注(IR)肠黏膜屏障功能的影响。方法 48只雄性SD大鼠,随机分为假手术(S)组、模型(IR)组、模型+生理盐水(IRS)组和模型+大黄素(IRE)组。IRE组给予40mg/(kg.d)大黄素灌胃,IRS组给予等量生理盐水灌胃,连续7 d,于第7天给药2 h后,制备肠缺血再灌注模型。光镜和透射电镜下分别观察各组小肠病理改变和紧密连接损伤,并进行Chiu’s评分。用TUNEL法检测肠黏膜细胞凋亡指数,Western Blot半定量法测定肠黏膜Claudin-1、Occludin蛋白含量。结果 IRE组与IR组、IRS组相比,小肠病理损伤和紧密连接结构破坏明显减轻,Chiu’s评分降低(P<0.05),细胞凋亡指数降低(P<0.05),两种连接蛋白Claudin-1、Occludin含量增加(P<0.05)。结论大黄素可以缓解肠缺血再灌注造成的肠道损伤、减少肠黏膜细胞凋亡、保护肠上皮细胞间紧密连接,对肠黏膜屏障具有保护作用。

Objective To investigate the effects of emodin on intestinal mucosal barrier in rat after in- testinal ischemia reperfusion. Methods Forty-eight male SD rats were randomly divided into four groups：sham control group （ S）, model group （ IR）, model ＋ saline group （ IRS）, model ＋ emodin group （IRE）. 40rag/（ kg·d） emodin was administrated intragastrically in IRE group for 7 days. The same volume saline was administra： ted intragastrically in IRS group. 2 hours after last administration. We established intestinal ischemia reperfusion model. Pathological changes of intestinal tissues and damages of tight junction were observed respectively by u- sing a light microscopy and a transmission electron microscopy in each group. Degree of injury to intestinal mu- cosa was evaluated by Chiu＇s assessment. Intestinal mucosal apoptotic index was measured by TUNEL staining. Semi-quantitative assessment of Claudin-1 and Occludin was measured by Western Blot. Results Pathological intestinal damages and tight junction damages were much lighter in IRE group than in IR group and IRS group. Degree of injury to intestinal mucosa and intestinal mucosal apoptotic index were significantly lower in IRE group than in IR group and IRS group （ all P 〈 0.05 ）. Contents of Claudin-1 and Occludin were significantly higher in IRE group than in IR group and IRS group （ all P 〈 0. 05 ）. Conclusion Emodin can alleviate intesti- nal pathological damages, reduce cell apoptosis, protect intercellular tight junction and intestinal mucosal barri- er in intestinal ischemia reperfusion rats.