GLP-1通过NOX4信号通路拮抗AGE诱导的人脐静脉内皮细胞氧化损伤  

Glucagon-like Peptide-1 Antagonized Oxidative Damage on Human Umbilical Vein Endothelial Cells Induced by Advanced Glycation Endproducts Through NOX4 Signaling Pathway

作　　者：孙慧琳[1] 黄志秋[1] 曾海龙[1] 张艺能 莫旭旭 陈宏[3] 

机构地区：[1]广东药学院附属第一医院内分泌科,广东广州510080 [2]广东药学院附属第一医院中心实验室,广东广州510080 [3]南方医科大学珠江医院内分泌科,广东广州510280

出　　处：《中山大学学报（医学科学版）》2016年第2期197-201,209,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金(S2011010002074);清远市科技计划(2011B011112044)

摘　　要：【目的】探讨NOX4信号通路在胰高血糖素样肽-1(GLP-1)拮抗糖基化终末产物(AGE)诱导的内皮细胞氧化损伤的作用机制。【方法】实验组分为对照组、AGE组、AGE+GLP-1组、AGE+NOX4 si RNA组及AGE+阴性si RNA组,RTPCR检测NOX4 m RNA表达,Western Blotting技术检测NOX4蛋白表达情况,流式细胞仪检测细胞凋亡率、ROS生成水平。【结果】与对照组相比,AGE可诱导细胞NOX4蛋白表达(P=0.001)及NOX4 m RNA表达(P<0.05)明显增高;加入GLP-1后,增高的NOX4蛋白(P=0.003)及NOX4 m RNA(P<0.05)明显下降。与AGE组相比,NOX4 si RNA可抑制AGE诱导的ROS生成(P=0.011)、细胞凋亡(P<0.05);阴性si RNA对AGE诱导的ROS生成(P=0.958)、细胞凋亡(P=0.169)无明显影响。【结论】GLP-1至少部分通过抑制NOX4蛋白表达拮抗AGE诱导的人脐静脉内皮细胞氧化损伤。[Objective] To discuss the role of NOX4 signaling pathway in the antagonistic mechanism of Glucagon-like Peptide-1 against the oxidative damage on vascular endothelial cells induced by advanced glycation endproducts. [ Method ] Experimental group was divided into a control group, AGE group, AGE ＋ GLP-1 group, AGE ＋NOX4 siRNA group and AGE ＋ negative control siRNA group. The expression of NOX4 mRNA was detected by RT-PCR. The expression of NOX4 protein was detected by Western blotting. The apoptosis rate and the levels of ROS were detected by flow cytometry. [Results] Compared with control group, AGE significantly promoted the expression of NOX4 protein （P = 0.001 ） and NOX4 mRNA （P 〈 0.05）. After added GLP-1 into the AGE group, it significantly inhibited the expression of NOX4 protein （P = 0.003 ） and NOX4 mRNA （P 〈 0.05）. Compared with AGE group, NOX4 siRNA inhibited the ROS generation （P = 0.011 ）, the apoptosis of endothelial cells （P 〈 0.05）. Negative control RNA had no influence on the ROS generation （P = 0.958）, the apoptosis of endothelial cells （P = 0.169）. [ Conclusion] GLP-1 antagonize oxidative damage on human umbilical endothelial cells induced by advanced glycation endproducts at least partly through inhibiting the expression of NOX4 protein.

关 键 词：胰高血糖素样肽-1 NOX4蛋白 人脐静脉内皮细胞 氧化损伤 

分 类 号：R78[医药卫生—口腔医学]