抗血小板制剂对家兔血管成形术后基质金属蛋白酶及其抑制剂表达的影响

The Effect on the Expression of Matrix Metalloproteinase and Its Inhibitor of Antiplalete Medicine in Rabbits after Angioplasty

观察抗血小板制剂西洛他唑对血管成形术后基质金属蛋白酶及组织型金属蛋白酶抑制剂表达的影响。建立家兔二次损伤的血管成形术模型 ,随机分为对照组、高脂组及西洛他唑组。观察血管成形术后 4周腹主动脉内膜增生情况 ,用免疫组织化学及逆转录聚合酶链反应检测基质金属蛋白酶 2和 9及组织型金属蛋白酶抑制剂 1和 2的蛋白及mRNA表达。结果发现 ,血管成形术 4周后 ,西洛他唑组新生内膜面积减少 ,管腔面积增大 ,与高脂组相比差异显著 ;基质金属蛋白酶 2和 9及组织型金属蛋白酶抑制剂 1和 2的蛋白及mRNA表达水平与高脂组相比明显减低。结果提示 ,抗血小板制剂西洛他唑可以抑制血管成形术后内膜基质金属蛋白酶及组织型金属蛋白酶抑制剂的表达 ,干预基质代谢 ,抑制内膜增生。

Aim To investigate the inhibitory effect of Cilostazol on matrix metalloproteinase-2 (MMP-2) and MMP-9 and tissue metalloproteinase inhibitor-1 (TIMP-1)and TIMP-2 protein and mRNA expression, to study its role and mechanism on proliferation after angioplasty. Methods 40 Japanese male white rabbits were injuried two times to make PTA models and divided into three groups: control group, high cholesterol group and Cilostazol group. PTA was proceeded under X-Ray, 4 weeks after the angioplasty, the damaged segments of abdominal arteries were harvested for morphometry (assessing NIA, MA, CA)and for immunohistochemical analysis as well as RT-PCR to evaluate MMP-2, MMP-9 and TIMP-1, TIMP-2 protein and mRNA expression level. Results Cilostazol can reduce the NIA and increase the CA. MMP-2, MMP-9 and TIMP-1, TIMP-2 protein and mRNA expression levels in high cholesterol control group increases at 4 th week after angioplasty. However, Cilostazol can reduce their levels. Conclusions Cilostazol can inhibit the vascular intimal hyperplasia, through its effect on the expression of MMP and TIMP to regulate the extracellular matrix turnover.