二烯丙基三硫化物包被支架术后冠状动脉管壁基质金属蛋白酶2及其抑制物表达的变化

Effects of Diallyl Trisulfide Coating Stent on the Expression of Metalloproteinase-2 and Tissue Inhibitor of Matrix Metalloproteinase-2 in a Canine Model of Coronary Restenosis

目的探讨二烯丙基三硫化物包被支架对犬冠状动脉基质金属蛋白酶2及基质金属蛋白酶组织抑制物2表达的影响。方法利用犬冠状动脉置入过大支架致内膜损伤,建立血管狭窄的动物模型。28个支架平分为基础对照组(单纯蛋白包被支架)和二烯丙基三硫化物治疗组(二烯丙基三硫化物包被支架),分别置入14只杂种犬的冠状动脉前降支或回旋支,未置入支架的另一支冠状动脉作为正常对照组(n=14)。在不同时点(5 h,1、7、14天和28天)处死动物,术后4周的血管标本做病理切片,部分组织抽提总RNA,应用RT-PCR方法测定不同时点冠状动脉壁内基质金属蛋白酶2和基质金属蛋白酶组织抑制物2的表达。结果与基础对照组相比,4周后二烯丙基三硫化物包被支架组显著抑制新生内膜的形成(P<0.01),面积狭窄率显著降低(P<0.01);与基础对照组相比,在5 h、1、14天和28天二烯丙基三硫化物包被支架显著抑制冠状动脉壁内基质金属蛋白酶2 mRNA的表达(P<0.05)。在5 h、1天和14天3个时点,二烯丙基三硫化物组与基础对照组基质金属蛋白酶组织抑制物2的表达差异无显著性;在7天和28天,二烯丙基三硫化物组基质金属蛋白酶组织抑制物2的表达明显高于对照组(P<0.05)。结论二烯丙基三硫化物包被支架明显抑制基质金属蛋白酶2基因的表达和增加基质金属蛋白酶组织抑制物2基因的表达,这可能是二烯丙基三硫化物抑制内膜增生的机制之一。

Aim To investigate the effect of diallyl trisulfide（DT）-coated coronary stents on expression of metalloproteinase-2（MMP-2） and tissue inhibitor of matrix metalloproteinase-2（TIMP-2） in canine model of restenosis.Methods DT-coated stents（210 μg/stent） were deployed with mild oversizing in the left circumflex coronary arteries（LCX） or the left anterior descending coronary arteries（LAD）of 14 canines.The implantation of protein-coated stents were used as control.Histopathologic examination was performed 28th days after stents implantation.Total RNA was isolated from the arterial wall at different time（5 h,1 d,7 d,14 d and 28 d） after stents implantation.RT-PCR method was adopted for detection of MMP-2 and TIMP-2 genes expression.Results Neointimal hyperplasia and the restenosis rate were less in DT-coated stents than those in control group（P0.01）.MMP-2 was constitutively expressed in uninjured coronary arteries,and its activity did not increase until 7 days and remained elevated up to 28 days after the implantation of protein-coated stents.MMP-2 genes expression in DT group was reduced at 5 h,1 d,14 d and 28 d compared with that in control groups（P0.01）.The expression of TIMP-2 genes was not significantly different at 5 h,1 d and 14 d after the implantation of DT-coated stents and protein-coated stents.At 7 d and 28 d,TIMP-2 genes expression increased in DT group compared with that in control groups（P0.05）.Conclusion DT-coated coronary stents can decrease the expression of MMP-2 and enhance the expression of TIMP-2 in the canine LAD or LCX after implantation,which could therefore contribute to decreasing the effects of its neointimal hyperplasia.