缬沙坦对兔动脉成形术后细胞凋亡及Bcl-2表达的影响

Effect of Valsartan on Expression of Bcl-2 and Apoptosis after Balloon Angioplasty in Rabbits

目的观察血管紧张素Ⅱ受体1亚型(AT1)拮抗剂缬沙坦对兔动脉成形术后血管内膜增生及平滑肌细胞凋亡的影响,探讨AT1受体拮抗剂治疗血管再狭窄的机制和作用。方法雄性新西兰白兔24只,随机分成3组:对照组始终以普通饲料12周,不加任何处理;模型组和缬沙坦组予高胆固醇喂养,4周后行腹主动脉内膜剥脱,继续高胆固醇饮食4周后行球囊成形术,模型组继续普通饲料饲养,而缬沙坦组给普通饲料+缬沙坦[10 mg/(kg.d)]喂养4周。12周末取腹主动脉行病理形态学观察,Tunel法检测血管平滑肌细胞凋亡,免疫组织化学分析Bcl-2。结果缬沙坦组较模型组模型组内膜厚度减少56.58%,内膜面积减少66.81%,平滑肌细胞凋亡显著增加(P<0.01),Bcl-2表达显著减少(P<0.01)。结论缬沙坦可以显著减轻兔腹主动脉成形术后内膜增生,其机制可能与抑制内膜损伤后Bcl-2表达水平,从而促进血管平滑肌细胞的凋亡有关。

Objective To investigate the effect of Valsartan （angiotensin Ⅱ type 1 receptor antagonists） on neointimal proliferation and Apoptosis after balloon angioplasty in rabbits. Methods Twenty-four male New Zealand white rabbits were randomly divided into three groups： The control group was always fed up with common diet; The model group and the valsartan group were fed up with hypercholesterolemic diet for 4 weeks,then they were underwent ballon angioplasty. During 4 weeks after operation, the model group was fed up with common diet,whereas the valsartan group was fed up with the admixture of valsartan （10 mg/kg · d） and common diet. The rabbits were killed at the end of the 12th week and the abdominal aorta was examined with pathologic and morphologic analysis, apoptosis was analyzed with Tunel method, and expression of Bcl-2 was analyzed with immunohistochemical method. Results： Compared with the model group, the valsartan group showed a decrease by 56.58% and 66.81% in the neointimal thickness and area. The apoptosis rate in valsartan group was significantly higher in vascular smooth muscle cells（P〈0. 01）, significantly lower in expression of Bcl-2 （P〈0.01）. Conclusion Valsartan could inhibit neointimal proliferation of rabbit＇s abdominal aorta after balloon injury and the mechanism might be correlated with its inhibiting expression of Bcl-2,and promoting apoptosis of vascular smooth muscle cells.