氯吡格雷对兔髂腹动脉球囊损伤后内膜增生的影响和机制研究  

Effect of clopidogrel on intimal hyperplasia of rabbit iliac artery after balloon injury and its mechanism

作　　者：任宏生[1] 朱兴雷[1] 张兴华[1] 楮熙[1] 宋尚名[1] 鹿克风[1] 李春梅[1] 刘旭杰[1] 苑海涛[1] 

机构地区：[1]山东大学山东省立医院心内科,山东济南250021

出　　处：《中华老年心脑血管病杂志》2006年第4期261-264,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：山东省科委自然基金(Y2002C47)

摘　　要：目的探讨抗血小板药氯吡格雷对兔髂腹动脉球囊损伤后内膜增生的影响和机制。方法37只新西兰兔随机分为正常对照组(7只)、模型组(10只)、氯吡格雷组(10只)和阿托伐他汀组(10只)。检测血脂和高敏C反应蛋白(hs-CRP)。观察动脉病理形态学改变,测量内膜、中膜厚度和面积,原位杂交检测血小板源性生长因子(PDGF)mRNA在髂动脉的表达,免疫组织化学染色测定凋亡蛋白bcl-2和bax的表达。结果与模型组比较,氯吡格雷组血清hs-CRP浓度、内膜/中膜厚度比、内膜/中膜面积比显著减少(P<0.05);髂动脉PDGFmRNA的表达明显降低(P<0.05),bcl-2表达下降不明显,bax表达明显升高,bcl-2/bax比值明显降低(P<0.05),氯吡格雷对血脂无明显影响。结论氯吡格雷减轻兔髂腹动脉球囊损伤后血管内膜增生,机制与降低动脉炎症反应,抑制PDGF表达和促进细胞凋亡有关。Objective To investigate the effect of clopidogrel on intimal hyperplasia of rabbit iliac artery after balloon injury and its mechanism. Methods Thirty seven New Zealand rabbits were allocated randomly to four groups： normal control group （ 7 ）, model group （10）, clopidogrel group （10） and atorvastatin group （10）. The blood lipid and high sensitivity C reactive protein（ hs-CRP） in all rabbits were examined at the beginning and the end of the experiment. All rabbits were sacrificed after 12 weeks and iliac arteries were removed. With HE staining, the artery morphology alteration was observed and the thickness and area of intima versus media were measured. The expression of platelet derived growth factor （PDGF）mRNA was observed by in situ hybridization method. Apeptosis gene bcl-2 and bax were tested by immunohistochemical staining. Results Compared with model group, the serum concentration of hs-CRP, the ratio of thickness of intima to media and that of area of intima to media in clopidogrel group were significantly decreased （ P 〈0. 05）. The expression of PDGF was notably decreased, bcl-2 was not reduced, the expression of bax was significantly increased and the ratio of bcl-2/ bax decreased significantly（ P 〈0. 05） in iliac artery of clopidogrel group. There was no difference between clopidogrel and atorvastatin groups. The clopidogrel group had no change in the level of blood lipid. Conclusion Clopidogrel can effectively relieve intimal hyperplasia of artery through reducing inflammatory reaction, inhibiting the PDGF expression and promoting the apeptosis of vascular smooth muscle cell.

关 键 词：冠状动脉硬化 血小板聚集抑制剂 血小板源性生长因子 细胞凋亡 血管内膜 

分 类 号：R543[医药卫生—心血管疾病]