复方丹参滴丸、普罗布考对动脉损伤后内膜增殖与血管重塑的影响

EFFECTS AND MECHANISM OF PROBUCOL AND FU FANG DAN SHEN DROPS ALONE AND IN COMBINATION ON NEOINTIMAL HYPERPLASIA AND VASCULAR REMODELING AFTER ENDOTHELIAL DENUTATION

目的:探讨复方丹参滴丸、普罗布考对兔髂动脉损伤后内膜增殖、血管重塑及血管内皮生长因子表达的影响。方法:雄性日本大耳白兔40只,随机平均分为对照组、普罗布考组、复方丹参滴丸组和联合组,高脂喂养两周后行髂动脉球囊内皮拉伤术,从术前3d开始对照组予单纯高脂喂养,治疗组分别以普罗布考(1.0g/只·d-1)、复方丹参滴丸(300mg/只·d-1)及两药联合灌喂至术后4周,取病变血管行病理形态学观察,免疫组化检测血管内皮生长因子(VEGF)和增殖细胞核抗原(PCNA)表达水平。结果:与对照组比较,普罗布考组、复方丹参滴丸组增殖内膜面积明显减小(P<0.05),普罗布考组内弹力膜包绕面积增大(P<0.05);与单独用药组比较,联合组内弹力膜包绕面积明显增大(P<0.05),但增殖内膜面积无改变(P>0.05);各治疗组VEGF、PCNA表达均较对照组明显减少(P<0.05)。结论:复方丹参滴丸、普罗布考均可抑制动脉损伤后平滑肌细胞增殖,减轻内膜增生;普罗布考兼有改善血管重塑的作用,两药联合使用可取得改善血管重塑的协同效应,其机制可能与减少VEGF在血管内、中膜的表达水平有关。

Objective：To explore the effects and mechanism of Probucol and Fu Fang Dan Shen Drops alone and in combination on neointimal hyperplasia and vascular remodeling after endothelial denutation. Methods：Forty male rabbits （body weight 2 000~2 300 g） were balloon injuried on the iliac artery after 2 weeks of a high-cholesterol diet （2 g cholesterol and 6 g peanut oil/d）, then were randomly assigned into four groups： Probucol（1 g/d, n =10）, Fu Fang Dan Shen Drops （300 mg/d, n =10）, combination （ n =10）, and control （no drug, n =10）. Each group administered drugs for 3 days before and was continued until the rabbits were killed 4 weeks after balloon injury. Morphometric analysis of the injured arteries included the intimal area, internal elastic lamina （IEL） area,and extral elastic lamina （EEL） area. Vascular endothelial growth factor （VEGF） and proliferating cell nuclear antigen （PCNA） protein levels in neointimal were studied by means of immunohistochemistry. Results：The neointimal area was less in Probucol group than in control group, however the IEL area was larger in Probucol group than in control group. As compared with control group, the neointimal area in Fu Fang Dan Shen Drops group was decreased. There was not significant difference in the neointimal area between combination group and Probucol or Fu Fang Dan Shen Drops group. But IEL area was larger in combination group than in Prbucol or Fu Fang Dan Shen Drpos group. The level of PCNA protein was decreased significantly in drug treating groups, however, there was not difference between combination group and the other treated groups. The level of VEGF was lower in drug treated groups than in control group. Conclusion：The therapy of Probucol or Fu Fang Dan Shen Drops can reduced the rabbit iliae artery neointimal hyperplasia induced by balloon injury, combined Probucol and Fu Fang Dang Shen Drops can achieve improvement in vascular remodeling more than use alone, perhaps the inhibition of VEGF expression in neointima perhaps is one of the mechanisms.