核因子κB受体活化因子配体对血管紧张素Ⅱ诱导人肾小球足细胞分泌血管内皮细胞生长因子的影响  

Effect of receptor activator of nuclear factor-κB ligand on the secretion of vascular endothelial cell growth factor from human glomerular podocytes induced by angiotensin Ⅱ

作　　者：齐悦[1] 朱涛[1] 覃志成[1] QI Yue1,ZHU Tao2,QIN Zhi-cheng3(The Second Hospital of Shanxi Medical University,Taiyuan 030001,Chin)

机构地区：[1]山西医科大学第二医院,山西太原030001

出　　处：《中国当代医药》2018年第14期13-16,20,共5页China Modern Medicine

基　　金：山西医科大学青年基金项目(057563);山西医科大学第二医院青年基金项目(20130101)

摘　　要：目的观察核因子κB受体活化因子配体(RANKL)对血管紧张素Ⅱ(AngⅡ)诱导的人肾足细胞分泌血管内皮细胞生长因子(VEGF)的影响,探究AngⅡ是否通过RANK/RANKL信号通路影响足细胞表达VEGF。方法以分化为树枝状的人肾足细胞为研究对象,以不同浓度(0、1、10、100 nmol/L)的AngⅡ处理,分别于不同时间(0、6、12、24 h)通过实时荧光定量PCR(RT-PCR)检测基因VEGF、RANK和RANKL的m RNA表达变化。然后以不同剂量的RANKL与100 nmol/L AngⅡ共同刺激足细胞24 h后,通过RT-PCR检测VEGF的m RNA表达变化,流式细胞术检测足细胞凋亡率变化。结果 AngⅡ呈剂量和时间依赖性地诱导足细胞表达VEGF、RANK和RANKL(P<0.05),而过量RANKL表现出剂量依赖性地阻断VEGF表达增高(P<0.05);与对照组比较,AngⅡ可以显著诱导足细胞凋亡(P<0.05),而RANKL可以抑制由AngⅡ诱导的足细胞凋亡(P<0.05)。结论 AngⅡ可能通过RANK/RANKL信号通路影响足细胞表达VEGF,RANKL通过反馈调节下调VEGF基因表达来抑制AngⅡ引起的足细胞凋亡,保护肾脏。Objective To investigate the effect of receptor activator of nuclear factor-κB ligand（RANKL） on the secretion of vascular endothelial growth factor（VEGF） induced by angiotensin Ⅱ（AngⅡ） in human renal podocytes,and to explore whether AngⅡaffecting VEGF expression in podocytes through RANK/RANKL signaling pathway.Methods The human renal podocytes differentiated into dendrites were selected as research subjects.They were dealt with Ang Ⅱ in different concentrations（0,1,10,100 nmol/L）.Real-time fluorescence quantitative PCR was performed at different time（0,6,12,24 h） to detect the changes in m RNA expression of the genes VEGF,RANK,and RANKL.Then podocytes were stimulated with different doses of RANKL and 100 nmol/LM AngⅡ for 24 h.The expression of VEGF m RNA was detected by RT-PCR and the apoptosis rate of podocytes was detected by flow cytometry.Results Ang Ⅱ induced podocyte expression of VEGF,RANK,and RANKL in a dose-and time-dependent manner（P〈0.05）,while excess RANKL showed dose-dependent blockade of VEGF expression increasing（P〈0.05）.Compared with the control group,AngⅡsignificantly induced podocyte apoptosis（P〈0.05）,while RANKL inhibited podocyte apoptosis induced by AngⅡ（P〈0.05）.Conclusion Ang Ⅱ may affect podocyte expression of VEGF through RANK/RANKL signaling pathway.RANKL inhibits the apoptosis of the podocytes induced by AngⅡ by regulating the expression of VEGF gene through feedback regulation and protects the kidneys.

关 键 词：足细胞 血管紧张素Ⅱ 核因子ΚB受体活化因子配体 血管内皮细胞生长因子 

分 类 号：R692.6[医药卫生—泌尿科学]