氯沙坦对晚期糖基化终产物诱导足细胞α-actinin-4表达的干预作用  

Effects of losartan on the expression of α-actinin-4 in podocytes induced by advanced glycation end-products

作　　者：成彩联[1] 郑振达[2] 石成钢[1] 叶增纯[1] 李灿明[1] 娄探奇[1] 

机构地区：[1]中山大学附属第三医院肾内科,广东广州510630 [2]中山大学附属第三医院心内科,广东广州510630

出　　处：《分子诊断与治疗杂志》2013年第6期367-370,共4页Journal of Molecular Diagnostics and Therapy

基　　金："十二五"国家科技支撑计划(2011BA110B05);国家自然科学基金(81070581);广东省科技厅基金资助项目(2011B080701005;2010B031600202)

摘　　要：目的观察晚期糖基化终产物(AGEs)对足细胞α-actinin-4的影响及氯沙坦的干预作用。方法不同浓度的AGEs(0,20,40,80μg/mL)干预足细胞24 h后,采用免疫印迹法检测足细胞α-actinin-4的表达。通过激光共聚焦显微镜观察足细胞肌动蛋白F-actin和α-actinin-4的分布,并在氯沙坦预处理足细胞后,观察α-actinin-4和F-actin的改变。结果与对照组相比,AGEs(80μg/mL)可明显降低足细胞α-actinin-4的表达[(62±13)%vs.100%,P<0.05],使α-actinin-4由膜周分布转为核周分布,并使肌动蛋白F-actin发生重构,而氯沙坦预处理可减轻AGEs介导的α-actinin-4的下调[(80±14)%vs.(62±13)%,P<0.05]和α-actinin-4和F-actin的重构,P<0.05。结论 AGEs可下调α-actinin-4表达,介导骨架蛋白的重构,而氯沙坦可减轻AGEs介导的这些改变。Objective To investigate the effects of advanced glycation end-products （AGEs） on the expression of α-actinin-4 and their mechanism. Methods Podocytes were incubated with different concentrations of AGEs for 24 hours, and the expression levels of α-actinin-4 were measured by western blot. The arrangement of α-actinin-4 and F-actin were observed by laser scanning confocal microscopy. Then podocytes were pretreated with losartan for 60 min before AGEs added. The changes of α-actinin-4 and cytoskeleton were observed. Results Incubation with AGEs （80μg/mL） resulted in a significant decrease in the expression ofα-actinin-4 [（62±13）%vs. 100%, P〈0.05], AGEs （80μg/mL） also induced bothα-actinin-4 and F-actin rearrangement. However, pretreatment with losartan （100 μmol/L） prevented the effects induced by AGEs in podocytes. Conclusion AGEs downregulate α-actinin-4 expression and induce cytoskeleton reorganization, and losartan prevent the changes induced by AGEs.

关 键 词：晚期糖基化终产物 足细胞 Α-ACTININ-4 

分 类 号：R965[医药卫生—药理学]