培哚普利在糖尿病大鼠肢体缺血后血管再生中的作用  

Effect of perindopril on neovascularization in ischemic hind limbs of diabetic rats

作　　者：高璐[1] 于德民[1] 

机构地区：[1]天津医科大学代谢病医院,卫生部与天津市激素与发育重点实验室,300210

出　　处：《中国糖尿病杂志》2009年第9期702-704,共3页Chinese Journal of Diabetes

摘　　要：目的探讨培哚普利在1型糖尿病(T1DM)大鼠肢体缺血后血管再生中的作用及相关机制。方法对T1DM大鼠模型予单侧肢体股动脉离断。分为对照(DM)组、培哚普利治疗(DMA)组和培哚普利+内皮型一氧化氮合酶(eNOS)阻断剂治疗(DML)组。治疗4周后比较各组缺血肢体血管再生情况以及eNOS、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)的mRNA和蛋白表达水平。结果与正常对照(NC)组相比,DM组的缺血肢体微血管密度(MVD)、eNOS、VEGF和bFGF的mRNA和蛋白表达均下降,DMA组上述指标明显上调(P均<0.05)。DML组的MVD、eNOS和bFGF的mRNA和蛋白表达降低(P<0.05),而VEGF表达不受影响(P>0.05)。结论 T1DM大鼠的缺血性血管再生受损,与之有关的生长因子表达下调。培哚普利能促进T1DM大鼠缺血肢体的血管再生,其机制与eNOS、VEGF和bFGF的表达上调有关。Objective To investigate the effect and related mechanisms of perindopril on angiogenesis in ischemic legs of diabetic rats. Methods Hind limbs ischemia was induced in diabetic rats by right femoral artery excision. DM rats with ischemic legs were randomly allocated into three groups： DM group, DM with perindopril treatment, and DM with perindopril and eNOS inhibitor for 4 weeks. The differences of angiogenesis, the mRNA and protein expressions of eNOS, VEGF and bFGF were observed after treatment. Results Compared with control group, the capillary density,the mRNA and protein expressions of eNOS, VEGF and bFGF in ischemic hind limbs of DM rats were decreased significantly,and administration of perindopril iraproved above indexes significantly （all P〈 0. 05）. In contrast, the combination of perindopril and eNOS inhibitor resulted in the decreased levels of capillary density,the mRNA and protein expressions of eNOS and bFGF（all P〈0.05） without significant changes in the VEGF mRNA and protein expression （P〈 0. 05）. Conclusions Diabetes mellitus reduces neovascularization and related growth factors expressions in rat ischemic legs. Treatment of perindopril improves angiogenesis in diabetic ischemic leg. This effect is related with the increase of expressions of eNOS, VEGF and bFGF.

关 键 词：培哚普利 肢体缺血 糖尿病 新生血管形成 

分 类 号：R587.1[医药卫生—内分泌]