法舒地尔对大鼠动脉粥样硬化斑块中单核细胞趋化蛋白-1表达的抑制作用  

The Influence of Rhokinase Inhibitor on the Expression of MCP-1 in the Atherosclerosis Plaque of Rats

作　　者：赵慧颖[1] 马小欣 陈冬梅[1] 

机构地区：[1]吉林大学第一医院心血管科,吉林长春130021 [2]宁波市李惠利医院

出　　处：《中国微循环》2009年第5期344-347,454,共5页Journal of Chinese Microcirculation

摘　　要：目的探讨Rho/Rho激酶途径在大鼠动脉粥样硬化形成过程中的作用及机制。方法将30只健康雄性Wistar大鼠(体质量220～250g),随机分为正常对照组、动脉硬化组和法舒地尔组,每组10只。正常对照组行假球囊损伤手术给予正常饮食,余两组每只大鼠给予30万U/kg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2%胆固醇、0.5%胆酸钠、0.2%丙基硫氧嘧啶、维生素D3粉剂(1.25×106U/kg饲料)、3%猪油等饲养。法舒地尔组同时给予法舒地尔5mg/kg体质量,每日2次腹腔注射。喂养9周后空腹24h抽血并处死,检测血脂水平,自主动脉弓下约1cm处留取动脉组织1cm用4%甲醛溶液固定,行HE染色,用免疫组织化学法检测斑块中血管紧张素Ⅱ-1型受体(AT1R)和单核细胞趋化蛋白-1(MCP-1)蛋白的表达。结果动脉硬化组均形成了典型的粥样斑块;免疫组化半定量分析表明:动脉硬化组与正常对照组和法舒地尔组比较,AT1R和MCP-1蛋白均明显升高(P<0.001),法舒地尔组与正常对照组比较,AT1R和MCP-1蛋白的表达也明显升高,有明显差异(P<0.05)。结论Rho/Rho激酶途径在大鼠动脉粥样硬化的形成过程中参与了重要的作用,该途径的激活与RAS系统的激活有密切关系,Rho激酶抑制剂的抗动脉粥样硬化作用可能是通过抑制了MCP-1的表达而起作用。Objective To linvestigate the Rho/Rho kinase path effect and mechanisms in the forming of rat atherogenesis. Methods 30 healthy male Wistar rats were randomly divided into 3 groups （250 - 300g） ： the normal group, the atherosclerosis group, the Rho-kinase inhibitor group, in each of which there were 10 rats. The normal control group undertook fake sacculus proprius damage and then offered normal diet. Each rat of the other three groups was given vitamin D3（3 10^5 u/kg feed） intramuscular injection first, then suffered artery drawing wound by sacculus proprius and was administrated with elementary feeder including 2% cholesterol, sodium cholate, 0.2% PTU. vitamin D3（ 1.25 10^6u/kg feed） and 3% lard. Dose and pathway for administration： 5mg/kg for Fasudil, abdominal cavity injection 2 times every day. After nine weeks, all the rats were killed and serum lipid level detected by drawing blood in empty stomach., slice about 1 cm below the aortic arch, then the arteries were fixed by 0.4% formaldehyde solution immediately, the expression of ATl R and MCP-1 in the vascular tissues were detected by immunohistochemistry method. Results The arteriosclerosis group formed typical atheromatous plaque; the semiquantitative method of immunohistochemistry indicates that the expression of AT1 R and MCP-1 in arteriosclerosis group was significantly higher than that of normal control and Fasudil groups（P 〈 0.001）; The expression of AT1 R and MCP-1 in the Fasudil group was significantly higher than that of the normal control group（ P 〈0.05）. Conclusion The Rho/Rho kinase path is significant in the forming process of rat arteriosclerosis, and the activation of Rho/Rho kinase path is related to the activation of rennin-angiotensin system. The inhibitor of Rho kinase has the role of inhibiting arteriosclerosis, which may be related to suppressing expression of MCP-1.

关 键 词：RHO激酶抑制剂 动脉粥样硬化 单核细胞趋化蛋白 

分 类 号：R543.1[医药卫生—心血管疾病]