卡维地洛抑制大鼠颈动脉损伤后MMP-2和IGF-1的表达  

Effect of carvedilol on the expression of MMP-2 and IGF-1 in carotid artery-injured rats

作　　者：袁向珍[1] 刘敏[1] 曹中朝[1] 王敏[1] 

机构地区：[1]内蒙古医科大学附属医院保健中心,内蒙古呼和浩特010050

出　　处：《广东药学院学报》2015年第2期253-257,共5页Academic Journal of Guangdong College of Pharmacy

基　　金：内蒙古自治区自然科学基金项目(2014MS08113)

摘　　要：目的观察卡维地洛（CAR）对大鼠颈动脉损伤血管组织基质金属蛋白酶2（MMP-2）、胰岛素样生长因子-1（IGF-1）表达的影响,探讨卡维地洛防治再狭窄的机制。方法雄性Wistar大鼠90只,随机分为假手术组、损伤组和CAR组,后两组行颈动脉球囊损伤术。3组均于术后1 d、3 d、7 d、14 d、28 d处死大鼠。光镜下观察血管损伤后内膜增生情况,用免疫组化和RT-PCR法检测MMP-2和IGF-1在各组术后不同时间点的表达情况。结果与损伤组比较,术后14 d CAR组内膜面积、内膜与中膜面积比值显著减少,管腔面积显著扩大（P〈0.05）;与损伤组比较,CAR组术后3~14 d MMP-2表达显著减少（P〈0.05）,7~28 d IGF-1表达显著降低（P〈0.05）。结论卡维地洛能有效抑制大鼠颈动脉损伤后MMP-2和IGF-1的表达,抑制血管平滑肌细胞（VSMC）迁移、增殖,降低内膜增生,从而减轻再狭窄。Objective To study the effect of carvedilol （CAR） on the expression of MMP-2 and IGF-1 in carotid artery-injured rats and explore the mechanism of carvedilol in prevention of restenosis. Methods Ninety Wistar rats were randomly divided into the sham-operated group, the injury group and the CAR group. The model of carotid balloon injury was established in the latter two groups. The rats were killed on 1,3,7, 14 and 28 days after injury. The intimal proliferation was observed by optical microscope. The expression of MMP-2 and IGF-1 at different time points was detected by immunohistochemistry and RT- PCR. Results The intimal area （IA） and ratio of intimal and medial area （IA/MA） in the CAR group were significantly lower than that in the injury group, while lumen area was higher than that in the injury group （P〈0.05）. Compared to the injury group, the expression of MMP-2 significantly decreased in the CAR group from 3 to 14 days after injury （ P〈 0.05 ）. Moreover, the expression of IGF-1 significantly decreased in the CAR group from 7 to 28 days after injury （P〈0.05）. Conclusion CAR could reduce restenosis,which may be related to inhibition of the expression of MMP-2 and IGF-1 in carotid artery- injured rats, VSMC migration and proliferation, and intimal hyperplasia.

关 键 词：卡维地洛 基质金属蛋白酶-2 胰岛素样生长因子-1 

分 类 号：R965[医药卫生—药理学]