沙格列汀对过氧化氢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通路影响的研究  

Effect of Saxagliptin on DDAH/ADMA/eNOS pathway in vascular endothelial cells injured by H_2O_2

作　　者：韩白玉[1] 卢岚敏[1] 张丽萍[1] 陈芳[1] 殷钢[1] 张勤颖[1] 

机构地区：[1]中国人民解放军第264医院内分泌科,太原030001

出　　处：《中国糖尿病杂志》2015年第11期1039-1042,共4页Chinese Journal of Diabetes

基　　金：解放军264医院院级基金(264YY201502)

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（HUVEC）作为靶细胞,在内皮细胞培养基中加入100μmol/L的H2O2制备细胞损伤模型,以20μmol/L沙格列汀进行干预,观察24~72h,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-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-Ⅱ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。Objective To investigate the effect of saxagliptin as a DPP-4inhibitor on DDAH/ADMA/eNOS pathway in human umbilical vein endothelial cells（HUVECs）injured by H2O2. Methods HUVECs were cultivated in culture medium containing 100 μmol/L H2O2 for establishing cell injury model.20μmol/L saxagliptin were applied for intervention.After 24~72h,concentrations of NO 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 level（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-Ⅱ protein expression level（P〈0.05）. Conclusion Saxagliptin can significantly improve the attenuated NO production in vascular endothelial cell induced by H2O2 by regulating DDAH/ADMA/eNOS pathway.

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 

分 类 号：R587.2[医药卫生—内分泌]