阿托伐他汀通过SIRT1/NADPH氧化酶对抗高糖诱导的人脐静脉内皮细胞的氧化损伤作用  被引量:8

Atorvastatin Inhibits High Glucose-induced Oxidative Stress Injury in Human Umbilical Vein Endothelial Cells by SIRT1/NADPH Oxidase Pathway

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作  者:曹娜[1] 葛力萁 程明月[1] 张卓琦[1] 王志荣[1] 

机构地区:[1]徐州医学院附属医院心内科,江苏省徐州市221000

出  处:《中国循环杂志》2014年第12期1000-1004,共5页Chinese Circulation Journal

基  金:江苏省兴卫工程医学重点人才资助项目(项目编号:RC 2007089)

摘  要:目的:探讨阿托伐他汀(atorvastatin,Atv)通过SIRT2沉默信息调节因子家族成员之一的SIRT1/还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶对高糖环境下人脐静脉内皮细胞(HUVECs)氧化损伤的作用。方法:人脐静脉内皮细胞株低糖(5.6 mmol/L)培养贴壁后随机分为正常组、渗透压对照组、高糖组、高糖+(0.1、1.0、10.0μmol/L)阿托伐他汀组、高糖+SIRT1抑制剂(sirtinol)组及高糖+NOX4抑制剂(apocynin)组,继续培养24 h后应用细胞计数试剂盒(CCK-8)检测细胞增殖,流式细胞仪检测细胞内活性氧(ROS)的水平,蛋白免疫印迹法检测细胞中SIRTl及NADPH氧化酶4(NOX4)的蛋白水平。结果:1与正常组相比,高糖各组细胞增殖减低,阿托伐他汀组均可改善高糖对HUVECs增值的抑制作用,呈浓度依赖性。2高糖环境下,细胞内ROS水平显著增加,NADPH氧化酶4的蛋白表达显著上调,SIRTl的蛋白表达明显降低。3阿托伐他汀可以上调高糖环境下SIRTl的表达,降低ROS、NADPH氧化酶4的表达,具有浓度依赖性。4高糖环境下,SIRTl抑制剂sirtinol可以降低SIRTl的表达,增加NADPH氧化酶4的表达,NADPH氧化酶4抑制剂apocynin可降低NADPH氧化酶4的表达,但对SIRT1的表达无明显影响。结论:阿托伐他汀可以对抗高糖诱导的HUVECs的氧化损伤,其可能的机制与升高内皮细胞SIRT1的表达有关,且SIRT1在NADPH氧化酶的上游发挥对抗高糖诱导的氧化损伤作用。Objective: To explore the effect of atorvastatin(Atv) on high glucose-induced oxidative stress injury in human umbilical vein endothelial cells(HUVECs) by SIRT1/NADPH oxidase pathway with the possible mechanisms.Methods: HUVECs were cultured in low glucose medium and then divided into 6 experimental groups: 1 Normal group, 2 Osmotic pressure control group, 3 High glucose(HG) group, 4 HG+ Atv(0.1, 1.0, 10.0) μmol/L group, 5 HG+sirtinol(SIRT1 inhibitor) group, 6 HG+apocynin(NOX4 inhibitor) group, and HUVECs were further cultured for 24 hours. The cell proliferation was examined by CCK-8 kit, ROS level was detected by flow cytometry method, protein expressions of SIRT1 and NOX4 were measured by Western blot analysis.Results: 1 Compared with Normal group, HG group had decreased HUVECs proliferation, Atv improved the HG inhibited proliferation in a does dependent manner. 2 HG group had the higher level of ROS, increased NOX4 protein expression and decreased SIRT1 protein expression. 3 In HG condition, Atv up-regulated SIRT1 expression and downregulated ROS and NOX4 expressions in a does dependent manner. 4 In HG condition, sirtinol decreased SIRT1 expression, increased NOX4 expression, and apocynin decreased NOX4 expression, while it had no influence on SIRT1 expression.Conclusion: Atorvastatin could resist HG-induced oxidative stress injury in HUVECs, which might be related to up-regulated SIRT1 expression, and SIRTI plays the role in NADPH oxidase at upstream.

关 键 词:高糖 阿托伐他汀 人脐静脉内皮细胞 氧化应激 SIRT1 NADPH氧化酶 

分 类 号:R541[医药卫生—心血管疾病]

 

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