Valsartan对Ⅱ型糖尿病小鼠炎症性血管损伤模型血管重建作用的影响

Effect of valsartan on remodeling of inflammatory vascular injury model in type 2 diabetic mouse

目的 :探讨血管紧张素Ⅱ型受体 (AT1 )拮抗剂Valsartan治疗糖尿病的作用及其机制。方法 :分别采用vanGieson染色及NIH分析软件分析新生内膜和中膜的面积、Brdu免疫组织化学染色计算Brdu指数 (DNA合成水平分析 )、TUNEL染色法计算凋亡指数和RT PCR法检测AT1 、AT2 受体及ACEmRNA表达水平 ,观察了Valsartan对Ⅱ型糖尿病小鼠炎症性血管损伤模型血管重建的影响。结果 :Valsartan除可显著抑制糖尿病KK Ay 小鼠血管内膜增生 ,显著抑制损伤血管的DNA合成 ,明显促进损伤血管的细胞凋亡 ,还对AT1 、AT2 受体及ACE的mRNA表达有明显的抑制作用。结论 :Val sartan治疗糖尿病、抑制动脉壁增厚的可能机制是 :一方面可能通过抑制肾素 血管紧张素系统发挥作用 。

Objective:To investigate the role of angiotensin Ⅱ type 1(AT1) receptor antagonist valsartan in diabetic mouse and its mechanism of action.Methods:Inflammation induced vascular injury was created by placing a polyethylene cuff around the femoral artery of KK A y mouse (type 2 diabetic mouse),and then valsartan (1 mg/kg per hour) was administered via abdominal implantation of micro pump for 7 14 days.Cuffed arteries were harvested and examined for neointimal and neomedial formation by van Gieson staining and NIH analysis software,DNA synthesis by Brdu immunohistochemistry,apoptosis by TUNEL staining,and AT1 and AT2 receptor and ACE mRNA by RT PCR.Results:In addition to the significant inhibition of intimal proliferation,DNA synthesis,and expressions of AT1 and AT2 receptor and ACE mRNA,valsartan treatment resulted in the apoptotic increase in the injured arteries of KK A y mice.Conclusion:The inhibitory effects of valsartan on thickening of inflammation induced arteries in KK A y mice could be implicated in inhibiting the function of renin angiotensin system,as well as in regulating the growth and apoptosis of vascular endotheliocytes.