培哚普利促进糖尿病大鼠缺血肢体的血管新生

Effect of Perindopril on the Improvement of Angiogenesis in Ischemic Legs of Diabetic Rats

目的探讨培哚普利在糖尿病大鼠肢体缺血后血管再生中的作用及相关机制。方法采用链脲佐菌素建立1型糖尿病大鼠模型,切断一侧肢体股动脉,分为对照组和培哚普利治疗组。治疗4周后观察各组缺血肢体血管新生情况。逆转录-多聚酶聚合链反应(RT-PCR)和Western印迹法测定后肢肌肉中内皮型一氧化氮合酶(eNOS)、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)的mRNA和蛋白表达,并测定结构型NOS(cNOS)活性。结果与正常对照组相比,糖尿病大鼠缺血肢体的微血管密度、eNOS、VEGF和bFGF的mRNA和蛋白表达及cNOS活性均下降。培哚普利治疗后上述指标均明显升高。结论糖尿病使大鼠缺血肢体的血管再生受损,有关的生长因子的表达下调或活性下降。培哚普利能促进糖尿病大鼠缺血肢体的血管再生,其机制与eNOS、VEGF和bFGF的表达上调及cNOS活性增加有关。

To analyze the effect and related mechanisms of Perindopril on reparative angiogenesis in ischemic legs of diabetic rats. Methods Type 1 Diabetic mellitus （DM） was induced in rats by injection of streptozotocin. Hind legs ischemia was then induced by right femoral artery excised. DM rats were then treated with or without Perindopril （2 mg/kg） for 4 weeks. The differences of angiogenesis, cNOS activity and the mRNA and protein expression of eNOS, VEGF and bFGF were observed at the end of experiment. Results Compared with control group, the capillary density, cNOS activity and the mRNA and protein expression of eNOS, VEGF and bFGF in ischemic hind legs of DM rats decreased significantly. Administration of perindopril enhanced above indexes significantly. Conclusions In Diabetic statement, reparative angiogenesis and the expression of growth factors in rat ischemic legs impaired. Perindopril can improve angiogenesis in diabetic ischemic legs. Reiated mechanism involved the increase of cNOS activity and the expression of eNOS, VEGF and bFGF.