整合素受体拮抗剂西仑吉肽对大鼠肠纤维化的治疗作用  

Therapeutic effect of integrin receptor antagonist cilengitide on intestinal fibrosis in rats

作　　者：陶庆松[1] 陈尧[1] 王宝偲[1] 郑宇[1] 

机构地区：[1]东南大学附属中大医院普外二科,江苏南京210089

出　　处：《中国普通外科杂志》2014年第10期1379-1384,共6页China Journal of General Surgery

基　　金：国家自然科学基金资助项目(81000153);江苏省自然科学基金资助项目(BK2010415)

摘　　要：目的:探讨整合素受体拮抗剂西仑吉肽对大鼠肠纤维化的治疗作用。方法:将21只SD大鼠随机均分为对照组、模型组、西仑吉肽治疗组,后两组采用三硝基苯磺酸(TNBS)+45%乙醇持续6周逐渐增量灌肠法诱导肠纤维化模型;西仑吉肽治疗组大鼠同时每日腹腔注射西仑吉肽,而其余两组则以同样的方式给予同体积的生理盐水。期间观察各组大鼠的一般情况,记录体质量的变化,6周后收集结肠标本,检测结肠炎症与胶原沉积情况、结肠组织中TGF-β1水平、以及I型胶原α1 mRNA与I型胶原蛋白水平。结果:除对照组外,另两组大鼠均出现一般情况不佳与体质量先减后增,但西仑吉肽治疗组大鼠一般情况好于模型组,且后期体质量增幅明显大于模型组(P<0.05);且两组大鼠结肠均有明显的慢性炎性病变与胶原纤维沉淀,但西仑吉肽治疗组组织病理学评分与胶原纤维含量均明显低于模型组(均P<0.05)。与对照组比较,另两组大鼠结肠组织总TGF-β1水平与活化型TGF-β1水平、以及I型胶原α1 mRNA与I型胶原蛋白水平均明显增加(均P>0.05),但西仑吉肽治疗组活化型TGF-β1水平、I型胶原α1 mRNA与I型胶原蛋白水平均明显低于模型组(均P<0.05)。结论:西仑吉肽能通过拮抗整合素受体抑制TGF-β1的活化,从而产生抗肠纤维化作用。Objective： rats. Methods： treatment To investigate the therapeutic effect of integrin receptor antagonist cilengitide on intestinal fibrosis in Twenty-one SD rats were equally randomized into control group, model group and cilengitide group, Intestinal fibrosis model was induced in rats in the latter two groups by continuousintracolonically injection with increasing doses of trinitrobenzene sulfonic acid （TNBS） in 45% ethanol solution for 6 weeks, and rats in cilengitide treatment group simultaneously received daily intraperitoneal injection of cilengitide, while those in the other two groups were given normal saline of the same volume in the same administration manner. During the experimental period, the general conditions were observed and the changes in body weight were recorded in each group of rats. The rat colonic tissue specimens were harvested after 6 weeks, the intestinal inflammation and collagen deposition were examined and the levels of TGF-β1, collagen type Iαl mRNA and collagen type I protein in colonic tissues were measured. Results： Except for control group, rats in the other two groups showed poor general conditions and an initial decrease and subsequent increase in body weight, but the general conditions in rats in cilengitide treatment group were better than those in model group, and the amplitude of later body weight gain in rats in cilengitide treatment group was significantly greater than that in model group （P〈0.05）; rats in these two groups had evident chronic inflammation and deposition of collagen fibers in the colonic tissues, but the histopathological score and collagen fiber content in cilengitide treatment group were significantly lower than those in model group （both P〈0.05）. Compared with control group, the colonic levels of total TGF-β1 and activated TGF-β1, and levels of collagen type Iαl mRNA and collagen type I protein were significantly increased in rats in the other two groups, but the levels of activated TGF-β1, collagen type Iαl mRNA and collage

关 键 词：结肠炎 纤维化 西仑吉肽 转化生长因子Β1 

分 类 号：R656.9[医药卫生—外科学]