p27Kip1在大鼠动脉粥样硬化斑块中的表达及法舒地尔的干预作用

目的 观察p27Kip1在大鼠动脉粥样硬化斑块中的表达及盐酸法舒地尔的干预作用.方法 将30只健康雄性Wistar大鼠随机分为三组:正常对照组、动脉粥样硬化组和法舒地尔组.正常对照组大鼠行假球囊损伤手术后给予正常饮食,动脉粥样硬化组和法舒地尔组大鼠给予维生素D3右下肢肌肉注射后用球囊行动脉拉伤,在基础饲料中加入胆固醇、胆酸钠、丙基硫氧嘧啶、维生素D3粉剂、猪油等饲养,法舒地尔组同时给予法舒地尔腹腔注射.喂养9周后抽血并处死,自主动脉弓下约1 cm处留取动脉组织行HE染色,用免疫组织化学法检测主动脉壁中Rho激酶和p27Kip1蛋白的表达.结果 HE染色显示,动脉粥样硬化组均形成了典型的粥样斑块;免疫组织化学检测发现,Rho激酶在正常的血管壁即有表达,在动脉粥样硬化组的表达明显高于正常对照组和法舒地尔组(P<0.01),在法舒地尔组的表达明显高于正常对照组(P<0.05).p27Kip1蛋白在正常血管壁表达较多,在动脉粥样硬化组的表达明显低于正常对照组和法舒地尔组(P<0.01),在法舒地尔组的表达明显低于正常对照组(P<0.05).结论 动脉粥样硬化病变时,粥样硬化灶内Rho激酶表达明显增加,p27Kip1蛋白的表达明显下调;法舒地尔明显抑制粥样硬化灶内的血管平滑肌细胞增殖,抑制Rho激酶的表达上调及p27Kip1蛋白的表达下调.

Expression of p27Kip1 in the Atherosclerotic Plaques of Rats and the Influence of Fasudil

Aim To investigate the expression of p27Kip1 in the atherosclerotic plaques of rats and fasudil hydrochloride intervention role. Methods 30 healthy male Wistar rats were randomly divided into three groups:normal control group,atherosclerosis group and fasudil group.Rats in normal control group were undertook fake sacculus proprius damage and then were offered normal diet.Rats in atherosclerosis group and fasudil group were given Vitamin D3 intramuscular injection first,then were suffered artery balloon injury and were fed with basic diet added cholesterol,sodium cholate,propylthiouracil,Vitamin D3 powder,lard.While rats in fasudil group were given the intraperitoneal injection of fasudil.After 9 weeks,all the rats were killed,the expression of Rho kinase and p27Kip1 protein in the vascular tissues were detected by immunohistochemistry method. Results The atherosclerosis group formed typical atherosclerotic plaque.Semi-quantitative immunohistochemical analysis showed that Rho kinase expressed in the normal vessel wall,and increased significantly in atherosclerosis group compared with that in the other two groups(P><0.01),Rho kinase expression in fasudil group also increased compared with that in normal control group(P><0.05).p27Kip1 protein expression in the normal vessel wall more,p27Kip1 protein expression in atherosclerosis group decreased significantly compared with that in the other two groups(P><0.01).p27Kip1 protein expression in fasudil group also decreased compared with that in the normal control group(P><0.05). Conclusion The expression of Rho kinase obviously increased and the expression of p27Kip1 protein obviously reduced in atherosclerotic lesions.Fasudil obviously inhibit vascular smooth muscle cell proliferation,inhibit the up-regulation of Rho kinase expression and down-regulation of the p27Kip1 protein in atherosclerotic lesions.