培哚普利对糖尿病大鼠后肢缺血性血管新生的作用及机制探讨  

Effect of perindopril on neovascniarization in ischemic hind limbs of diabetic rats and investigation of its mechanism

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糖尿病足科,卫生部与天津市激素与发育重点实验室,300070

出　　处：《中华内分泌代谢杂志》2009年第4期426-428,共3页Chinese Journal of Endocrinology and Metabolism

基　　金：天津医科大学科学基金（2006KY34）

摘　　要：目的探讨糖尿病大鼠后肢缺血性血管新生受损的原因、培哚普利在缺血后血管新生中的作用及可能机制。方法将单侧后肢缺血的糖尿病大鼠随机分为对照组、培哚普利组、培哚普利＋一氧化氮合酶（NOS）阻断剂组、培哚普利＋缓激肽-Ⅰ型受体（BK—B1R）拮抗剂组。治疗4周后比较各组缺血肢体血管再生情况以及内皮型NOS（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、结构型NOS（cNOS）活性和一氧化氮（NO）含量。结果与对照组相比，糖尿病组的缺血肢体微血管密度（MVD）、eNOS、VEGF和bFGF的mRNA和蛋白表达、cNOS活性和NO含量均下降，培哚普利治疗组上述指标显著上调（P〈0．05）。联合BK—B1R拮抗剂使上述指标明显降低（P〈0．05）；联合NOS阻断剂治疗使MVD、eNOS和bFGF表达、cNOS活性和NO含量下降（P〈0．05），而VEGF表达不受影响（P〉0．05）。结论糖尿病状态下大鼠缺血肢体的血管新生和相关生长因子的表达及活性受损。培哚普利对糖尿病大鼠肢体缺血性血管新生具有促进作用，这种作用至少部分由BK-B1R所介导，其机制涉及了VEGF／eNOS／bFGF的激活。Objective To investigate the cause of impaired angiogenesis in diabetic ischemic hind limbs of rats and the role and related mechanisms of angiotensin-converting enzyme inhibitor（ACEI）perindopnil in postischemic revascularization. Methods Hind limbs ischemia was induced in diabetic rats by excisison of the right femoral artery. Diabetic rats were randomly allocated to one of the following treatments for 4 weeks： perindopril, perindopril plus NOS inhibitor, perindopril plus bradykinin B1 receptor（BK-B1R） antagonist or saline. The differences in angiogenesis, mRNA and protein expressions of eNOS, VEGF, and bFGF, cNOS activity and NO content were observed after treatments. Results Compared with the control rats, capillary density,mRNA,and protein expression of eNOS,VEGF,and bFGF in ischemic hind limbs of diabetic rats were decreased significantly（P〈0. 05）. Administration of perindopril enhanced the above indexes significantly（P〈 0.05 ）. The combination of BK-B1R antagonist rendered the above indexes decreased significantly （P〈 0. 05）. In contrast, the combination of NOS inhibitor decreased eNOS and bFGF expression, NO content, and eNOS activity, while the expression of VEGF didn＇t change. Conclusions Neovascularization and related growth factors expression and activity decreased in diabetic rat ischemic limbs. Treatment of perindopril improved postischemic revascularization. This effect was mediated, at least in part, by the BK-B1R-related pathway, and the activation of VEGF/eNOS/bFGF signals may be involved in the proangiogenic effect.

关 键 词：血管紧张素转换酶抑制剂 培哚普利 肢体缺血 糖尿病 新生血管形成 

分 类 号：R686[医药卫生—骨科学]