帕立骨化醇对糖尿病肾病大鼠肾保护作用机制研究  

Renoprotective effect of paricalcitol in rats with diabetic nephropathy

作　　者：兰凯[1] 张光伟 倪菁[1] 常远[1] 张渭民 

机构地区：[1]西安医学院临床医学院,陕西西安710021

出　　处：《西部医学》2017年第11期1488-1491,共4页Medical Journal of West China

基　　金：陕西省教育厅科研计划项目(16JK1657)

摘　　要：目的探讨帕立骨化醇对糖尿病肾病(DN)大鼠的肾保护作用机制。方法采用链尿佐菌素(STZ)腹腔注射的方法构建DN大鼠动物模型,将造模成功的大鼠随机分为帕立骨化醇组(P组)、DN组(D组),并设置健康对照组(N组)。P组大鼠每周灌胃帕立骨化醇3次,每次0.4μg/kg;D组与N组给予等量丙二醇灌胃。给药12周后检测各组24h尿蛋白定量及血生化指标,通过ELISA法检测肾组织中肾素浓度变化,尿中前列腺素E2(PGE2)水平,免疫组化法检测肾组织中环氧化酶-2(COX-2)和nephrin蛋白的表达。结果与N组相比,D组和P组24h尿蛋白定量、血清肌酐、肾素、尿PGE2水平及COX-2表达较高,P组又显著低于D组,差异均有统计学意义(P<0.05)。与N组相比,D组和P组nephrin蛋白表达较低,P组又显著高于D组,差异均有统计学意义(P<0.05)。结论帕立骨化醇可显著减少DN大鼠早期蛋白尿,此作用可能通过抑制COX-2、PGE2,减少肾素分泌,上调足细胞nephrin蛋白的表达实现。Objective To investigate the renoprotective effect of paricalcitol in rats with diabetic nephropathy（DN）and its mechanism.Methods DN model rats were established by intraperitoneal injection with streptozotocin（STZ）.The DN rats were randomly divided into the paricalcitol group（group P）and DN group（group D）.Healthy rats were chosen as healthy control（group N）.Group P were treated with 0.4μg/kg paricalcitol t.i.w.Group D and group N were given equal amount of 1,2-Propanediol by gavage.24-h urinary protein and serum biochemical indicators were examined after 12 weeks.ELISA methods were applied to detect the concentration change of renin in the kidney,urine levels of prostaglandin E 2（PGE 2）.Immunohistochemistry were applied to detect the protein of COX-2 and nephrin.Results Compared with those of group N,24-h urinary protein,serum creatinine,renin,PGE 2 and COX-2 of D group and P group were markedly increased,and they were significantly higher in group D than that in group P（P〈0.05）.Compared with that of group N,the expression of nephrin in group D and group P was markedly decreased,and lower expression was found in group D（P〈0.05）.Conclusion Paricalcitol can significantly reduce the proteinuria in rats with diabetic nephropathy,which may be associated with down-regulation of COX-2,PGE 2 and renin expression,up-regulate the protein expression of podocin of podocyte.

关 键 词：糖尿病肾病大鼠 肾保护 帕立骨化醇 

分 类 号：R587.2[医药卫生—内分泌]