卡维地洛对大鼠颈动脉损伤后MMP-9和TIMP-1表达的影响

目的：观察卡维地洛（CAR）对大鼠颈动脉损伤血管组织MMP-9、TIMP-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。三组均于术后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-9、TIMP-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3-14d MMP-9表达显著减少（P〈0.05）,而TIMP-1表达无显著变化。结论：卡维地洛有效抑制大鼠颈动脉损伤后MMP-9表达,抑制了VSMCs迁移、增殖,改善了细胞外基质的合成与降解平衡,从而减轻再狭窄。

EFFECTS OF CARVEDILOL ON THE EXPRESSION OF MMP-9 AND TIMP-1 IN CAROTID ARTERY-INJURED RATS

Objective： To study the effects of carvedilol（ CAR） on the the expression of MMP- 9and TIMP-1 in carotid artery-injured rats and explore the mechanisms of carvedilol in prevention of restenosis. Methods： 90 Wistar rats were randomly divided into sham-operated group,injury group and CAR group,and the model of carotid balloon injury were established in the latter two groups. The rats were killed on the 1 st、3 rd、7 th、14 th、28 th day after injury. The intimal proliferation was observed by optical microscope. The expression of MMP-9 and TIMP-1 at different time points were detected by the method of immunohistochemistry and RT-PCR. Results： The intimal area（ IA） and ratio of intimal and medial area（ IA / MA） in CAR group were significantly lower than those in injury group,while lumen area was higer than its in injury group（ P〈0. 05）. Compared to injury group,the expression of MMP-9 significantly decreased in CAR group at 3 rd to 14 th day after injury（ P〈0. 05）. While the expression of TIMP-1 had no difference between two groups. Conclusion： CAR could reduce restenosis,the mechanism of which may be inhibit the expression of MMP-9 in carotid artery-injured rats,VSMCs migration and proliferation and improve balance of synthesis and degradation of extracellular matrix.