二甲双胍对内皮细胞血管紧张素II受体1表达的影响  

Effect of metformin on type 1 angiotensin II receptor expression in endothelial cells

作　　者：张栩[1] 于文[2] 王孝勇[1] 管庆波[1] 赵家军[1] 

机构地区：[1]山东大学附属省立医院内分泌科,济南250021 [2]滨州市人民医院内分泌科,山东滨州256606

出　　处：《山东大学学报（医学版）》2010年第11期1-6,11,共7页Journal of Shandong University:Health Sciences

基　　金：山东省优秀中青年科学家奖励基金资助项目(2006BS03012);山东省医药卫生科技发展计划资助项目(2009HW058);2008山东省人事厅留学人员科技活动项目择优经费资助项目

摘　　要：目的观察二甲双胍对内皮细胞1型血管紧张素II受体(AT1R)表达的影响并探讨其机制。方法应用western-blot检测内皮细胞AT1R、腺苷酸活化蛋白激酶α亚基(AMPKα)、核转录因子κB抑制蛋白(I-κB)的表达,应用激光共聚焦观察核转录因子κB(NF-κB)P65在细胞核内变化,比色法测定各组内皮细胞培养液乳酸脱氢酶(LDH)活性。同时应用RNA干扰技术,进一步观察I-κB、AMPKα的作用。结果二甲双胍显著减少肿瘤坏死因子α(TNFα)诱导的内皮细胞AT1R的蛋白表达(P<0.01),显著降低I-κB的磷酸化(P<0.01),同时二甲双胍显著降低内皮细胞培养液LDH活性(P<0.01),而AMPKαSiRNA干预后,二甲双胍对内皮细胞AT1R的影响作用显著减弱(P<0.01)。结论二甲双胍通过促使AMPKα磷酸化,激活AMPKα信号通路,抑制NF-κB活化和内皮细胞AT1R的表达,减轻内皮细胞损伤,保护内皮细胞功能,从而发挥其对心血管的有益作用。Objective To observe the effect of metformin on type 1 angiotensin II receptor （ AT1R） expression in endothelial cells and investigate its mechanism. Methods AT1 R,inhibitor protein κB （ I-κB） and AM P-activated protein kinase α（ AM PKα ） protein expressions in endothelial cells were determined by Western blot,and nuclear factor-κB （ NF-κB） activation in endothelial cells was observed by con-focal laser scanning microscopy. The lactate dehydrogenase （ LDH） activation in the culture medium was detected by colorimetric assay. Also,the roles of NF-κB and AM PKα in the effect of metformin on AT1 R were determined by RNA interference technology. Results I-κB phosphorylation and AT1 R protein expression induced by tumor necrosis factor α （ TNFα） in endothelial cells were significantly reduced by metformin,and LDH activity in the endothelial cell culture medium was significantly decreased （ P 〈 0. 01） . The inhibitory effect of metformin on AT1 R expression in endothelial cells was significantly reversed by AM PKαSiRNA （ P 〈 0. 01） . Conclusion NF-κB activation and AT1 R expression can be inhibited by the intervention of metformin,and activation of the AM PKα pathway plays an important role in the beneficial effect of metformin on cardiovascular endothelial cells.

关 键 词：二甲双胍 内皮细胞 血管紧张素II受体1 腺苷酸活化蛋白激酶α 核转录因子ΚB 

分 类 号：R364.5[医药卫生—病理学]