二甲双胍联合利拉鲁肽对棕榈酸诱导的内皮细胞氧化损伤具有协同保护作用  

Synergistically protective effects of metformin and liraglutide on endothelial cell oxidative damage induced by palmitic acid

作　　者：柯静[1] 魏蕊[1] 刘烨[1] 杨进[1] 田勍[1] 张琳[1] 王广[1] 洪天配[1] 

机构地区：[1]北京大学第三医院内分泌科,100191

出　　处：《中华糖尿病杂志》2014年第5期312-316,共5页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：国家973计划资助项目（2012CB517502）;国家自然科学基金资助项目（81070701,81000315,81270858）;高等教育博士学科点新教师基金资助项目（20120001120069）

摘　　要：目的 探讨二甲双胍和利拉鲁肽在改善棕榈酸诱导的人脐静脉内皮细胞氧化损伤方面是否具有协同保护效应.方法 分离培养人脐静脉内皮细胞,应用不同浓度棕榈酸处理诱导细胞氧化损伤,观察不同浓度二甲双胍和（或）利拉鲁肽对细胞氧化损伤的影响.流式细胞仪检测细胞内的活性氧簇（ROS）水平,硝酸还原酶法检测上清一氧化氮（NO）的水平,组间比较采用单因素方差分析和Q检验.结果 与对照组相比,0.25和0.50 mmoL/L棕榈酸细胞内ROS水平显著升高[（125±17）％、（189±8）％比100％,P＜0.05],上清NO水平降低[（89.9±6.2）％、（79.8±4.8）％比100.0％,P＜0.05];二甲双胍（0.5 ～ 1.0 mmol/L）和利拉鲁肽（10 ～ 100 nmol/L）单独应用后,可使0.50 mmol/L棕榈酸所致的ROS产生增加和NO产生减低作用下降;低剂量的二甲双胍（0.1 mmol/L）或利拉鲁肽（3 nmoL/L）单独应用对0.5 mmol/L棕榈酸的作用均无明显的影响,但两者联合则可减低上述作用：两者联合组与棕榈酸组相比,ROS水平降低[（158±31）％比（250±27）％,P＜0.05],NO水平增加[（91.7±30.6）％比（82.3±5.0）％,P＜0.05].结论 二甲双胍和利拉鲁肽在改善棕榈酸诱导的内皮细胞氧化损伤方面具有协同效应.Objective To investigate whether metformin and liraglutide had a synergistically protective effects on palmitic acid-induced endothelial cell oxidative damage.Methods Human umbilical endothelial cell,which were exposed to palmitic acid for inducing endothelial cell dysfunction,were treated with metformin and/or liraglutide for 24 h.Intracellular level of reactive oxygen species （ROS） was detected by flow cytometry.Supernatant nitric oxide （NO） concentration was measured by nitrate reductase method.One-way ANOVA and Q test were applied to analyze the differences among the groups.Results Compared with control group,0.25 and 0.50 mmol/L palmitic acid significantly increased intracellular ROS levels （（125 ± 17） %,（189 ± 8） % vs 100%,P 〈 0.05）,and decreased supernatant NO levels （（89.9 ± 6.2） %,（79.8 ± 4.8） % vs 100.0%,P 〈 0.05）.Either metformin （0.5-1.0 mmol/L） or liraglutide （10-100 nmol/L） treatment alone could significantly prevent the augmented ROS levels and reduced NO levels induced by 0.5 mmol/L palmitic acid.Mono-treatment with low dose of metformin （0.1 mmol/L） or liraglutide （3 nmol/L） did not alter the effects of 0.5 mmol/L palmitic acid on ROS and NO production.However,combination treatment with these doses of the agents significantly prevented the increased ROS levels and decreased NO levels induced by 0.5 mmol/L palmitic acid,shown as decrease of ROS level （（158±31）% vs （250±27）%,P〈0.05） and increase of NO level （（91.7 ±30.6）% vs （82.3± 5.0）%,P 〈 0.05）.Conclusion Metformin and liraglutide have a synergistic effects in protecting endothelial cell from palmitic acid-induced oxidative damage.

关 键 词：二甲双胍 利拉鲁肽 内皮细胞 氧化应激 

分 类 号：R587.1[医药卫生—内分泌]