罗格列酮对髂动脉球囊损伤兔血管内皮的保护作用

Protective effects of rosiglitazone on vascular endothelial function after balloon endothelial denudation of iliac artery in rabbits

目的探讨罗格列酮(RGZ)对髂动脉球囊损伤兔血管内皮的保护作用及其机制。方法 30只雄性新西兰大耳白兔随机分为正常对照组(普通饮食)、模型组(高脂饮食+球囊损伤)和RGZ组(高脂饮食+球囊损伤+RGZ)。喂养8周后行髂动脉球囊内膜剥脱术,建立兔髂动脉血管内皮损伤模型,RGZ组从术前3天开始给药,0.5mg·kg_(-1)·d_(-1)术后4周分别测定血脂、血糖、hsC-RP、-氧化氨(NO)、一氧化氮合酶(NOS)和内皮素1(ET一1),取髂动脉标本行病理形态学观察,免疫组化法测定增殖细胞核抗原(PCNA)的表达,TUNEL法检测细胞凋亡。结果与模型组动物相比,罗格列酮组在术后4周末TC、TG、LDL-C、ET-1等指标均明显降低(P<0.01或P<0.05),HE及PCNA染色提示内膜增殖程度显著减轻(P<0.01),细胞凋亡率明显减少(P<0.05)。结论罗格列酮对球囊损伤后的血管内皮有保护作用,其机制可能与调脂、抑制血管平滑肌细胞的增殖和迁移并促进其凋亡、影响NOS/ET-1的分泌等途径有关。

Objective To investigate the protective effects of rosiglitazone on vascular endothelial {unction after balloon endothelial denudation in rabbits and the underlying mechanism. Methods Thirty male New Zealand white rabbits were randomly divided into control （normal diet） ,model （hypercholesterol diet plus balloon endothelial denudation ） and rosiglitazone groups （model supplemented with rosiglitazone）. Iliac arteries were injured by balloon endothelial denudation in model and rosiglitazone groups. Rosiglitazone was administrated to therapy group. Serum FPG, lipids, hs-CRP, NO, NOS and ET-1 levels were measured at 4 weeks after balloon endothelial injury. The local iliac arteries were sectioned for analysis of pathological morphology and were stained for PCNA immunohistochemcal analysis. And the apoptosis rate of smooth muscle cells was examined with Tunnel method. Results The model of balloon endothelial denudation was successfully induced. After rosiglitazone intervention, levels of serum TC, TG, LDL-C, ET-1 had significant diffierence between model and rosiglitazone groups （P〈0.01 or P〈0. 01）. The intimal area （IA）, medial area （MA）, and intimal proliferation index of rosiglitazone group were significantly lower than in model group （P〈0.05）. The expression of PCNA in rosiglitazone group was significantly lower than in model group. The apoptosis rate of rosiglitazone group was significantly increased as compared with that of model group （P 〈 0.01 ）. Conclusions Rosiglitazone could efficiently protect the vascular endothelial function from balloon injury. The protective mechanism may relate to lowering lipids, inhibiting the proliferation of vascular smooth muscle cells and promoting their apoptosis, and regulating the activity of NOS and secretion of NO and ET-1.