三种抗血小板方案对兔颈动脉移植静脉桥内膜增殖抑制作用的比较

Inhibitory effect of three anti-platelet therapy strategies on neointimal hyperplasia in rabbits after autologous vein graft

目的建立兔自体静脉移植模型,比较阿司匹林、氯吡格雷、阿司匹林联合氯吡格雷三种抗血小板方案对移植静脉内膜增殖的影响。方法 32只新西兰大白兔随机分为4组,每组8只,设为空白对照组和药物组。建立模型后喂养6个月,采集标本,行病理和电镜观察,测量并计算新生内膜及中膜面积;免疫组化观察Bax和Bcl-2表达,计算细胞增殖指数。结果氯吡格雷组和阿司匹林联合氯吡格雷组之间的内膜与中膜的厚度及面积比、细胞增殖指数、Bcl-2表达阳性率均无显著差异,但均分别低于空白对照组和阿司匹林组,空白对照组和阿司匹林组之间无显著差异。Bax蛋白表达在各组中的差异无统计学意义。结论动物试验显示氯吡格雷能抑制移植静脉平滑肌细胞和内膜的增生,与阿司匹林联合应用不能增强其抑制作用,单用阿司匹林无抑制作用。

Objective To construct the autologous vein graft model of rabbits and compare the inhibitory effect of three anti-platelet therapy strategies on neointimal hyperplasia in rabbits after autologous vein graft.Methods Thirty-two New Zealand rabbits were randomly divided into aspirin group,clopidogrel group,aspirin plus clopidogrel group,and control group,8 rabbits in each group.After an animal model was established,the rabbits were fed for 6 months.Samples were collected and examined under microscope.Areas of new intima and media were calculated.Expression of Bax and Bcl-2 was detected with immunohistochemistry.Proliferation index of cells was counted.Results The thickness between new intima and media,ratio of areas,proliferation index of cells,and positive Bcl-2 expression were not statistical different between clopidogrel and aspirin plus clopidogrel groups,and were lower than those in control and aspirin groups.No statistical difference was found in expression of Bax protein among the 4 groups.Conclusion Clopidogrel can effectively inhibit the proliferation of vein smooth muscle cells and intima,clopidogrel plus aspirin does not increase the inhibitory effect on neointimal hyperplasia,and aspirin alone has no inhibitory effect on neointimal hyperplasia,in rabbits after autologous vein graft.