罗格列酮联合洛沙坦对糖尿病肾病大鼠足细胞的协同保护作用

目的探讨罗格列酮联合洛沙坦对糖尿肾病(DN)大鼠足细胞的协同保护作用。方法制备DN大鼠模型,将动物随机分为DN模型组、罗格列酮干预组、洛少坦干预组及罗格列酮联合洛沙坦干预组,另设正常对照组。8周后观察尿蛋白排泄量,采用免疫组化、RT-PCR方法检测肾皮质nephrin、podocin蛋白及mRNA表达,采用透射电镜检测足细胞超微结构变化。结果(1)各干预组DN鼠尿蛋白排泄均减少。(2)联合干预组对足细胞超微结构及nephrin、podocin下调的改善作用优于单药干预组。结论罗格列酮与洛沙坦联合用药对DN大鼠肾脏保护作用优于单种药物治疗,其机制部分与改善足细胞超微结构及上调nephrin、podocin表达有关。

Study on the protective effect of combination of Rogiglitazone and Losartan on thepodocytes of diabetic nephropath rats

Objective To investigate the protective effect of the combination of rosiglitazone and losartan on thepodocytes of diabetic nephropathy(DN) rats.Methods A rat model of DN was established.The DN rats were randomized to DN model group,rosiglitazone-treatef group,losartan-treated group,or combined treatmentgroup.24h urine protein excretion was determined,the ultrastructure of podocytes was measured under eletron microscopy,and the expressions of nephrin and podocin were detected by immunohistochemisty ans RT-PCR after 8weeks.Results A decrease in 24h urine protein excretion occurred in all treatment groups.Better improvement on the ultrastructure of the podocytes ans on the downnegulation of nephrin and podocin expressions developed in the combined treatment group than in rosiglitazone or losartan-treated group.Conclusion The protective effect of rosiglitazone combined with losartan on the kidney of the DN rats is superior to the agents used separately,whose mechanism may be partly related with the upregulation of the expressions of the nephrin and podocin,and with imprrovement of the ultrastructure of pdocytes.