辛伐他汀对颈总动脉损伤大鼠血管基质金属蛋白酶-2与基质金属蛋白酶抑制因子-2表达的影响

Effects of simvastatin on the expression of matrix metalloproteinase-2 and inhibitor of metalloproteinase-2 in rats with injury of common carotid artery

目的观察辛伐他汀对颈总动脉损伤大鼠血管壁基质金属蛋白酶-2(MMP-2)及其特异性的抑制剂基质金属蛋白酶抑制因子-2(TIMP-2)表达的影响。方法取18只大鼠采用颈总动脉挤压术制备血管狭窄模型,设假手术组、手术组和辛伐他汀组,每组6只大鼠。术后14 d观察颈总动脉形态学变化,胶原纤维的改变,免疫组织化学方法观察颈总动脉MMP-2及TIMP-2的表达。结果假手术组颈总动脉各层结构正常,清晰,无明显的胶原纤维沉积及血管平滑肌细胞(VSMC)增殖迁移;手术组大鼠颈总动脉中胶原纤维大量增多沉积,VSMC增殖迁移;辛伐他汀组胶原纤维沉积程度降低,VSMC增殖迁移程度也降低。与假手术组相比,手术组MMP-2与TIMP-2表达的平均光密度值升高,MMP-2/TIMP-2比值降低,差别均有统计学意义(P<0.01);与手术组相比,辛伐他汀组MMP-2与TIMP-2表达的平均光密度值降低,MMP-2/TIMP-2比值升高(P<0.01)。结论 MMP-2/TIMP-2比值降低是导致胶原纤维沉积进而引起术后血管再狭窄的重要因素,辛伐他汀能通过提高MMP-2/TIMP-2比值,减轻血管再狭窄的程度。

Objective To observe the effects of simvastatin on the expression of matrix metalloproteinase-2（MMP-2） and tissue inhibitor of metalloproteinases-2（TIMP-2） in rats with injury of common carotid artery.Methods The angiostegnosis model was established by pressurization of arteria carotis communis in 18 rats,which were divided into sham operation group,operation group,simvastatin group,six rats in each group.At the 14th day after operation,morphologic changes and collagen fibrous changes were observed,and the expression of MMP-2 and TIMP-2 was detected by immunohistochemical method.Results In sham operation group,the structures in each layer of carotid arteries of the rats were normal and clear.There were not obvious accumulation of collagen fibers and proliferation and transference of vascular smooth muscle cell（VSMC）.In operation group,a great quantity of collagen fibers accumulated in the carotid arteries and the VSMC proliferated and transfer of the rats.In simvastatin group,the extent of accumulation of collagen fibers lowered,and so was the degree of proliferation and transference of VSMC.Compared with sham operation group,the expression of MMP-2 and TIMP-2 was significantly increased in operation group（P0.01）,and the ratio of MMP-2/TIMP-2 was obviously decreased（P0.01）.Compared with operation group,the expression of MMP-2 and TIMP-2 was significantly decreased in simvastatin group（P0.01）,the ratio of MMP-2/TIMP-2 was obviously increased（P0.01）.Conclusion Decrease in the ratio of MMP-2/TIMP-2 is a main factor of accumulation of caliginous fibers and angei-restenosis after operation,and simvastatin can reduce the extent through raising the ratio of MMP-2/TIMP-2.