晚期糖基化终产物对足细胞内肾素-血管紧张素系统-第三军医大学学报.docVIP

晚期糖基化终产物对足细胞内肾素-血管紧张素系统的影响 成彩联，郑振达，石成钢，叶增纯，刘 迅，娄探奇 （510630 广州，中山大学附属第三医院肾内科） [摘要] 目的 观察晚期糖基化终产物（AGEs）对足细胞内肾素-血管紧张素系统（RAS）的影响及作用机制。方法 不同浓度的AGEs干预小鼠足细胞24 h，分别检测肾素renin、血管紧张素原AGT、血管紧张素Ⅱ 1型、2型受体AT1R、AT2R的表达，血管紧张素转换酶ACE的活性和血管紧张素ⅡAng Ⅱ的浓度，观察蛋白激酶BAkt的μg/mL）明显上调AGT和AT1R的表达[ 183.0±19.0% vs 100%，179.0±17.0% vs 100%，P0.05]，裂解液中ACE活性明显增加[（142.8±10.3）U/μg vs （85.0±9.2）U/μg，P0.05]，细胞上清中Ang Ⅱ的浓度明显增加[11.2±0.8 pg/ml vs.（7.0±0.7 pg/ml，P0.05]；Akt的磷酸化上调100%P0.05，而LY294002可减轻AGEs介导的足细胞内RAS的激活；与AGEs组相比，LY294002可改善AGEs介导的足细胞粘附性的下降[（82±13）% vs 40±12%；78±14% vs42±13%，P0.05]。结论 AGEs可能通过磷酸肌醇3激酶途径激活足细胞内的RAS，降低足细胞粘附性。 [关键词] 晚期糖基化终产物；磷酸肌醇3激酶；足细胞；肾素-血管紧张素系统 [中图法分类号][文献标志码] A [基金项目] “十二五”国家科技支撑计划（2011BA110B05）；国家自然科学基金（座机电话号码）；广东省科技厅基金资助项目（2011B0座机电话号码，2010B0座机电话号码） [通信作者] 娄探奇，E-mail:Lou.taq@163.com Effects of advanced glycation end products on renin-angiotensin system in podocytes Cheng Cailian, Zheng Zhenda, Shi Chenggang, Ye Zengchun, Liu xun, Lou Tanqi Department of nephropathy, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, china Abstract Objective To investigate the effects and mechanisms of advanced glycation end products AGEs on the components of the renin-angiotensin system RAS in podocytes. Methods Immortalized mouse podocytes were exposed to various concentrations of AGEs for 24 hours. The expression levels of renin, angiotensinogen AGT, angiotensin II type 1 and 2 receptors AT1R and AT2R , angiotensin II Ang II levels , and angiotensin-converting enzyme ACE activity were assayed, both Akt and phosphorylated Akt were examined by western blot; Podocyte adhesion was measured when podocytes were pretreated with phosphoinositide 3-kinasePI3-K inhibitor LY294002, losartan, captopril, and chymastatin, respectively. Results Treatment with AGEs resulted in significant increases in the expression of AGT and AT1R. Moreover, ACE activity and Ang II levels increased significantly. However, there were no changes in renin or AT2R expression. AGEs did increase the