辛伐他汀对大鼠克罗恩病结肠纤维连接蛋白表达的影响

摘要

目的:观察辛伐他汀对大鼠克罗恩病(Crohn's disease,CD)结肠纤维连接蛋白(fibronectin,FN)表达的影响和机制.方法:采用2,4,6-三硝酸苯磺酸(TNBS)灌肠制备大鼠克罗恩病模型.SD大鼠分为对照组、模型组、辛伐他汀(5、20 mg/kg)组,21 d后进行结肠组织学和纤维化评分；RT-PCR测定结肠组织中FN、FN ED-A及FN ED-B mRNA,Western blot检测FN及p-MYPT-1(Rho激酶活化的标志)蛋白表达.结果:与对照组相比,模型大鼠结肠组织学和纤维化评分明显升高,FN表达增多(P＜0.01),辛伐他汀干预后,结肠纤维化评分、FN及p-MYPT-1的表达均下降(P＜0.05).结论:辛伐他汀能抑制TNBS诱导的大鼠结肠炎结肠FN的表达,其机制可能与抑制Rho激酶活化有关,提示辛伐他汀对CD肠纤维有抑制作用.%Objective:To investigate the effect and mechanism of simvastatin on fibronectin expression in the colon of rate with Crohn's disease (CD). Methods:The CD model was established in rats by intracolonic administration of 2,4,6-trinitrobenzene sulphonic acid (TNBS). SD rats were divided into the control group,model group,model group with simvastatin (5,20 mg/kg) group. Colonic histologic and librotic scores were assessed after 21 days. RT-PCR was used to delect the mRNA expression of FN, FN ED-A and FN ED-B. Western blotting was used to detect the protein expression of FN and p-MYPT-1 (representing activity of Rho-kinase). Results:In comparison with the control group,the score of histology and flbrosis.and the expression of FN and p-MYPT-1 in colonic tissue were increased obviously in the model group (P < 0.01),and reduced after administration of simvastatin (P< 0.05). Conclusions:Simvastatin is effective in preventing colonic FN expression in TNBS-induced colitis,which may result from the inhibition of the activity of Rho-kinase. It is suggested thai simvastatin may prevent intestinal fibrosis in CD.