复方丹参滴丸预防兔血管再狭窄的实验研究

The Experiment Study on Composite Denshen Pilulae(CDP) in Prevention of Restenosis in Rabbits

目的探讨复方丹参滴丸预防再狭窄的可能机制.方法健康成年二级雄性日本大耳白兔30只,体重2.5～3.0公斤.随机分为三组:正常对照组10只,模型组10只(球囊内膜剥脱加高胆固醇饮食),治疗组10只(球囊内膜剥脱加高胆固醇饮食以及复方丹参滴丸150mg/d).八周后处死各组动物,取兔的髂动脉标本行病理形态学观察以及采用免疫组化方法分析基质金属蛋白酶(MMPs)MMP2,MMP9的表达.结果 (1)复方丹参滴丸组较模型组,血管腔直径狭窄减轻27.8%;内膜厚度减少41%,内膜面积减少52%,内膜厚度和中膜厚度比减少22%、面积比减少38%,各组之间有显著性差异(P＜0.01).(2)模型组和对照组比较其MMP2、MMP9明显增加,复方丹参滴丸组和模型组相比,复方丹参滴丸组MMP-2、MMP-9的表达低于模型组.(3)内膜的增生以及管腔的狭窄程度与MMP2、MMP9有很好的相关性(γ=0.896P＜0.01).结论 MMP在再狭窄形成中起了重要的作用;复方丹参滴丸能够明显抑制血管损伤后的内膜增生.

Objeetive To investigate the mechanism of CDP in prearention and treatment of restenesis in rabbits. Methods 30 white male rabbits were randomly divided into 3 groups： control group（n= 10）; model group（whose intima was destroyed by balloon and was given hypercholesteroic diet, n= 10） and treatment group （whose intima was destroyed by ballon and was given hypercholesteroie diet plus CDP 150mg/d, n = 10）. After 8 weeks, rabbits were killed and the local iliac arteries were sectioned for analysis of pathological morphology and immunohistochemistry analysis [ the expression of metalloproteinases （MMPs） MMP2, MMP9 ]. Angiogram of iliac artery was performed in all rabbits. Results （1） According to the angiogram of iliac artery, the stenesis of artery lumen diameter decreased 27.8% in treatment group compared with model group, According to automatic pathological morphology analysis, the thickness of intima decreased 41% and intima area decreased 52% in the treatment group compared with the model group. The intima thickness/medium thickness of arteries ratio decreased 22%, the area ratio decreased 38% in treatment group compared with the model group （ P 〈 0.01）. （2）Aeeording to the immunohis to chemistry analysis, the expressions of MMP2, MMP9） were 11.3 ± 3.65, 17.2 ± 1.88 in control group, 23.4 ± 4.61, 28.2 ± 2.38 in model group and 16.2 ± 3.03, 20.1 ± 4.01 in treatment group. The expressions of MMP2 and MMP9 were higher in model group than in control group. And the expressions of MMP2 and MMP9 were significandy lower in treatment group than in model group（ P 〈 0.01）. （3）The thickening of vascular neointima and stenosis degree ofvascolar lumen were correlated well with MMP2, MMP9 （r = 0.896, P 〈 0.01）. Conclusions MMP and TIMP （metalloproteinase inhibitors） play very important role in the restenosis process of artery. CDP can inhibit the thickness of vascular neointima after balloon injury.