南方医科大学学报2016,Vol.36Issue(12):1727-1731,5.DOI:10.3969/j.issn.1673-4254.2016.12.24
LY294002抑制PI3K/Akt信号通路阻断地塞米松降尿蛋白的作用
LY294002 blocks the effect of dexamethasone in reducing urine protein in rats by inhibiting PI3K/Akt signaling pathway
摘要
Abstract
Objective To investigate the involvement of PI3K/Akt signaling pathway in the changes of urine protein in adriamycin-induced nephropathic rats treated with dexamethasone and LY294002 (a PI3K inhibitor).Methods SD rats were randomized into normal control group,ariamycin-induced nephropathy group (ADR group),ariamycin + dexamethasone group (DEX group),and ADR+DEX+LY294002 group (LY294002 group).On days 7,14 and 28 after the treatments,24-h urine was collected from the rats to analyze the total urine proteins.The renal tissues were obtained on day 28 to examine the expressions of p-AKT,AKT and Bad proteins in the cortical tissues using Western blotting;the expression of Bad mRNA in the cortical tissues was measured by QPCR.Results Urine protein increased progressively in ADR group accompanied by significantly reduced p-AKT/AKT ratio and increased Bad mRNA expression in comparison with those in the normal control group (P<0.05).Urine protein was obviously reduced in DEX group with comparable p-AKT/AKT ratio and Bad mRNA expression level with those in the control group (P>0.05).Urine protein showed no significant reduction in LY294002 group,but the p-AKT/AKT ratio was significantly reduced and Bad mRNA expression was increased compared with those in DEX group (P<0.05).Conclusion Dexamethasone increases the expression of Bad mRNA and reduces urine protein in adriamycin-induced nephropathic rats by activating PI3K/Akt signaling pathway.LY294002 can inhibit PI3K/Akt signaling pathway to block the effect of dexamethasone,suggesting that PI3K/Akt signaling pathwayis one of the signaling pathways that mediate the effect of dexamethasone on proteinuria.关键词
LY294002/PI3K/Akt信号通路/阿霉素肾病大鼠/蛋白尿/地塞米松Key words
LY294002/PI3K/Akt signaling pathway/adriamycin-induced nephropathy/proteinuria/dexamethasone引用本文复制引用
周志刚,吴汪丽,刘甜甜,彭云,劳文芹,梁敏,朱美华..LY294002抑制PI3K/Akt信号通路阻断地塞米松降尿蛋白的作用[J].南方医科大学学报,2016,36(12):1727-1731,5.基金项目
广东省医学科研基金(A2014307) (A2014307)