【摘要】 目的 观察二肽基肽酶-4(DPP-4)抑制剂沙格列汀对过氧化氢(H2O2)诱导损伤的血管内皮细胞分泌一氧化氮(NO)及内皮素-1(ET-1)的影响。 方法 以培养人脐静脉内皮细胞株(HUVEC)作为靶细胞，在内皮细胞培养基中加入100 µmol/L H2O2制备细胞损伤模型，以不同浓度沙格列汀(5、10、20、40 µmol/L)进行干预，观察不同培养时间(0、12、24、36 h)各浓度组的差异。分别采用硝酸还原酶法和放射免疫法法检测细胞上清液中NO及ET-1含量。 结果 H2O2作用HUVEC后，细胞上清NO含量降低，而ET-1含量升高(P<0.05)。各浓度沙格列汀组NO含量均高于模型组(100 µmol/L H2O2)，而ET-1含量降低，这种作用在一定剂量范围内随药物剂量增加而增强，在一定时间范围内随时间增加而增强(P<0.05)。 结论 沙格列汀可改善H2O2引起的血管内皮细胞NO、ET-1分泌异常。

　　【关键词】 沙格列汀;血管内皮细胞;一氧化氮;内皮素

　　【Abstract】 Objective To investigate the effect of DPP-4 inhibitor saxagliptin on the release of nitric oxide (NO) and endothelin-1 (ET-1) secreted by injured human umbilical vein endothelial cells (HUVECs) induced by H2O2. Methods HUVECs were cultivated in culture medium containing 100 µmol/L H2O2 to established cell injury model. Various doses of saxagliptin (5、10、20、40 µmol/L)were applied to intervention. The concentration of NO and ET-1 in the supernatant of HUVECs was detected respectively at different time points(0、12、24、36 h). Result The concentration of NO was decreased and the secretion of ET-1 was increased induced by H2O2(P<0.05). The concentration of NO were higher in all groups with different concentration of saxagliptin than in model group(100 µmol/L H2O2), but the concentration of ET-1 were not(P<0.05). Moreover, the improvment of saxagliptin was dose-dependent and time-dependent within a certain dose range and a certain time range (P<0.05). Conclusion Saxagliptin could improve the abnormal release of NO and ET-1 induced by HUVECs.

　　【Key words】 Saxagliptin; Human umbilical vein endothelial cells; Nitric Oxide; Endothelin-1