沙格列汀改善过氧化氢诱导损伤的血管内皮细胞一氧化氮和内皮素-1分泌异常的观察

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引起血管内皮细胞NO、ET-1分泌异常.

The effect of DPP-4 inhibitor saxagliptin on improving the H2O2-induced secretion abnormality of NO and ET-1 of vascular endothelial cells

Objective To investigate the effect of DPP-4 inhibitor saxagliptin on improving the H2O2-induced secretion abnormality of NO and ET-1 of human umbilical vein endothelial cells （HUVECs）.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 for intervention.The concentration of NO and ET1 in the supernatant of HUVECs was detected respectively at different time points（0,12,24,36 h）.Results H2 O2 could significantly inhibits the synthesis of NO and increase the secretion of ET-1（P＜0.05）.Saxagliptin could significantly increase the secretion of NO and decrease the secretion of ET-1.Moreover,the improving effect of saxagliptin was in dose-and timedependent manner within a certain dose and time range （P＜0.05）.Conclusion Saxagliptin improves the release of NO and inhibit the release of ET-1 from HUVECs so that it exerts protective effect on HUVECs.