【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二甲基精氨酸二甲胺水解酶/非对称性二甲基精氨酸/内源性一氧化氮合酶(DDAH/ADMA/eNOS)通路的影响。 方法  以培养人脐静脉内皮细胞株(H1ⅣEC)作为靶细胞，在内皮细胞培养基中加入100 umol/L的H2O2制备细胞损伤模型，以20μmol/L沙格列汀进行干预，观察24～72 h，检测细胞上清一氧化氮(NO)含量、ADMA浓度，检测细胞中NOS活性、DDAH活性及DDAH蛋白表达量。 结果  H2O2作用HUVEC后，细胞上清中NO含量降低，而ADMA浓度增加(P<0.05)。细胞中NOS活性、DDAH活性、DDAH一Ⅱ蛋白表达量降低(P<0.05)；而加入沙格列汀，细胞上清中NO含量升高，ADMA浓度降低(P<0.05)。细胞中NOS活性、DDAH活性、DDAH一1I蛋白表达量升高(P<0.05)。 结论   沙格列汀通过对DDAH／ADMA／eNOS通路的调节作用改善H2O2诱导的内皮细胞NO生成减少。
     【关键词】 沙格列汀；血管内皮细胞；二甲基精氨酸二甲胺水解酶；非对称性二甲基精氨酸；一氧化氮；一氧化氮合酶

     【Abstract】 Objective   To investigate the effect of saxagliptin as a DPP_4 inhibitor on DDAH/ADMA/eNOS pathway in human umbilical vein endothelial cells(HUVECs)injured by H2O2． Methods   HUVECs were cultivated in culture medium containing 100 umol/L H2O2 for establishing eell injurymodel．20 μmol/L saxagliptin were applied for intervention．After 24～72 h，concentrations of N0 and ADMA in the supernatant of HUVECs were detected respectively at different time points．Activity of eNOS and DDAH in cells was detected and protein expression level of DDAH was also detected．Results    H2O2 could significantly increase the level of ADMA (P<0.05)，and decreased NO concentration in the
medium and the intracellular eNOS and DDAH activity as well as DDAH—II protein expression 1evel(P<0.05)．Saxagliptin could significantly decrease the level of ADMA(P<0.05) and increase NO concentration in the medium and the intracellular NOS and DDAH activity as well as DDAH一Ⅱproteinexpression 1evel(P<0.05)． Conclusion   Saxagliptin can significantly improve the attenuated NO production in vascular endothetial eell induced by H2 02 by regulating DDAH/ADMA/eNOS pathway．

    【Key words】Saxagliptin；Vascular endothelial cells；Dimethylarginine dimethylaminohydrolase (DDAH)；Asymmetric dimethylarginine (ADMA)；Nitric oxide (NO)；Nitric oxide sythase (NOS)