沙利度胺对膜性肾病大鼠肾足细胞VEGF、PLA2R、podocin蛋白及其mRNA表达水平的影响  

Effects of Thalidomide on Expression Levels of VEGF,PLA2R,Podocin Protein and mRNA in Podocytes of Rats with Membranous Nephropathy

作　　者：高宏宇 张国英 刘秋菊[2] 王晔 张莉 陈超 GAO Hongyu;ZHANG Guoying;LIU Qiuju(Department of Nephrology,Second Hospital of Baoding,Hebei,Baoding,071000)

机构地区：[1]河北省保定市第二医院肾病科,保定071000 [2]河北大学附属医院肾内科,保定071000

出　　处：《中国中西医结合肾病杂志》2020年第6期481-484,I0002,共5页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：保定市科技局立项项目(No.18ZF013)。

摘　　要：目的:探讨沙利度胺对膜性肾病(MN)大鼠VEGF、PLA2R、podocin及其mRNA表达水平的影响。方法:将48只SD大鼠随机分为对照组、模型组、沙利度胺组和来氟米特组各12只,应用自备阳离子化牛血清白蛋白制备MN大鼠模型。沙利度胺组给予沙利度胺溶液(100 mg/kg)灌胃,来氟米特组给予来氟米特(5 mg/kg)灌胃。治疗4周后,测定血肌酐、尿素氮、尿微量蛋白、IL-1β、IL-6和TNF-α水平;取对数生长期大鼠肾足细胞加入含有10%对应大鼠血清的培养液培养,CCK-8法检测各组细胞增殖;RT-PCR和Western Blot测定各组细胞VEGF、PLA2R、podocin蛋白和mRNA的表达。结果:与对照组相比,模型组大鼠的尿微量白蛋白、尿素氮、肌酐、IL-1β、IL-6、TNF-α、VEGF、PLA2R水平升高(P<0.05),肾足细胞存活率和podocin表达下降(P<0.05);与模型组相比,沙利度胺组和来氟米特组大鼠的尿微量白蛋白、尿素氮、肌酐、IL-1β、IL-6、TNF-α、VEGF、PLA2R水平降低(P<0.05),肾足细胞存活率和podocin表达增加(P<0.05)。结论:沙利度胺可能通过抑制肾足细胞VEGF、PLA2R的表达,上调podocin的表达,改善MN大鼠的肾组织结构和功能损伤。Objective:To explore effects of thalidomide on expression levels of VEGF,PLA2R,podocin and their mRNA in lesion tissues of membranous nephropathy(MN)rats.Methods:48 SD rats were randomly divided into control group,model group,thalidomide group and leflunomide group,12 cases in each group.Self-made cationization bovine serum albumin was performed to prepare MN rat models.The thalidomide group was administered with thalidomide solution(100 mg/kg).The leflunomide group was administered with leflunomide(5 mg/kg).After 4 weeks of treatment,levels of serum creatinine,blood urea nitrogen,urine microprotein,IL-1β,IL-6 and TNF-αwere measured.Rat podocyte cells at logarithmic growth stage were cultured in medium containing 10%of the rat serum,and cell proliferation was detected by CCK-8.RT-PCR and Western Blot were performed to measure expression of VEGF,PLA2R,podocin protein and mRNA in podocytes.Results:Compared with control group,after treatment,levels of urinary microprotein,blood urea nitrogen,creatinine,IL-1β,IL-6,TNF-α,VEGF and PLA2R were increased in model group(P<0.05),the survival rate of renal podocytes and expression of podocin decreased(P<0.05).Compared with model group,after treatment,levels of urinary microprotein,blood urea nitrogen,creatinine,IL-1β,IL-6,TNF-α,VEGF and PLA2R were decreased in thalidomide group and leflunomide group(P<0.05),the survival rate of renal podocytes and expression of podocin increased(P<0.05).Conclusion:Thalidomide may improve renal tissue structure and function damage in MN rats by inhibiting expression of VEGF and PLA2R and up-regulating expression of podocin in podocytes.

关 键 词：沙利度胺 膜性肾病 血管内皮生长因子 磷脂酶A2 受体 PODOCIN 

分 类 号：R692[医药卫生—泌尿科学]