奥美沙坦酯对糖尿病肾病大鼠肾脏保护作用及对肾组织Nephrin、VEGF表达的影响  

Protective effect of olmesartan on kidney and expression of Nephrin and VEGF in diabetic nephropathy rats

作　　者：朱晓娜 王玉环[1] 吴娟娟[1] 董鹏[1] 张敏[2] ZHU Xiaona;WANG Yuhuan;WU Juanjuan;DONG Peng;ZHANG Min(The Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China)

机构地区：[1]西安交通大学第二附属医院,西安710004 [2]西安医学院第一附属医院

出　　处：《山东医药》2019年第14期15-18,共4页Shandong Medical Journal

基　　金：陕西省西安市科技计划医学攻关项目(SF1316)

摘　　要：目的观察奥美沙坦酯干预对糖尿病肾病(DN)大鼠肾脏的保护作用,及其对肾组织足细胞标志性蛋白Nephrin和血管内皮生长因子(VEGF)表达的影响。方法将30只大鼠随机分为NC组10只和实验组20只,实验组腹腔注射链脲佐菌素制作DN模型;将18只成功造模大鼠随机分为两组各9只,OM组予以奥美沙坦酯10 mg/kg灌胃,DN组予以0. 5%羟甲基纤维素钠灌胃;干预8周后,收集24 h尿液检测尿蛋白,禁食不禁水后尾静脉取血检测血肌酐(Scr)及尿素氮(BUN);麻醉后剖腹取肾脏,行HE和PAS染色观察肾脏病理改变,采用RT-PCR及Western blotting法分别检测肾组织Nephrin、VEGF mRNA及蛋白。结果 DN组24 h尿蛋白、Scr、BUN水平较NC组升高,OM组24 h尿蛋白、Scr、BUN水平较DN组降低(P均<0. 05)。NC组肾脏组织结构正常,DN组肾小球基底膜增厚及系膜基质增加,OM组肾小球基底膜增厚及系膜基质增加程度较DN组减轻。与NC组比较,DN组肾组织Nephrin mRNA及蛋白表达减少而VEGF mRNA及蛋白表达增加(P均<0. 05);与DN组比较,OM组肾组织Nephrin mRNA及蛋白表达增加而VEGF mRNA及蛋白表达减少(P均<0. 05)。结论奥美沙坦酯通过下调VEGF表达保护DN大鼠足细胞,从而减少尿蛋白排泄,保护肾脏功能。Objective To observe the protective effect of olmesartan on the kidney of diabetic nephropathy (DN) rats,and its effect on the expression of Nephrin and vascular endothelial growth factor (VEGF) in podocytes of kidney tissues. Methods Thirty rats were randomly divided into the NC group (10 rats) and experimental group (20 rats).DN model was made by intraperitoneal injection of streptozotocin (STZ) in the experimental group.Eighteen successful DN rat models were randomly divided into two groups,with 9 in each.Omesartan 10 mg/kg was given to OM group and 0.5% hydroxymethyl cellulose sodium was given to DN group.After 8 weeks of intervention,24-hour urine was collected to detect urinary protein,blood was taken from caudal vein after fasting water to detect serum creatinine (Scr) and urea nitrogen (BUN),kidney was taken by caesarean section after anesthesia,and renal pathological changes were observed by HE and PAS staining.Nephrin,vascular endothelial growth factor (VEGF) mRNA and protein in the kidney tissues were detected by RT-PCR and Western blotting,respectively. Results The 24-hour urinary protein,Scr and BUN levels in the DN group were higher than those in the NC group,while those in the OM group were lower than those in the DN group (all P < 0.05 ).The glomerular basement membrane and mesangial matrix increased in the DN group and OM group.The increased degree of glomerular basement membrane and mesangial matrix in the OM group was less than that in the DN group.Compared with NC group,the expression of Nephrin mRNA and protein in the DN group decreased while the expression of VEGF mRNA and protein increased (all P <0.05).Compared with the DN group,the expression of Nephrin mRNA and protein in the OM group increased,while the expression of VEGF mRNA and protein decreased (all P <0.05). Conclusion Olmesartan has protective effect on podocytes in DN rats by down-regulating the expression of VEGF,thereby reducing the excretion of proteinuria and protecting renal function.

关 键 词：糖尿病肾病 奥美沙坦酯 肾功能 足细胞 Nephrin蛋白 血管内皮生长因子 大鼠 

分 类 号：R587[医药卫生—内分泌]