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目的探讨洛沙坦对糖尿病肾病(DN)大鼠足细胞超微结构及其相关分子 nephrin、podocin 表达的影响。方法制备 DN 大鼠模型,随机将动物分为 DN 模型组、干预组,另设时照组;干预组给予洛沙坦50mg/(kg·d);于第4、8周检测24 h 尿蛋白量、用免疫组化、RT-PCR 方法检测肾皮质 nephrin、podocin 蛋白及 mRNA 表达,用透射电镜检测足细胞超微结构变化。结果模型组24 h 尿蛋白排泄增多(P<0.01),足细胞数减少、足突增宽,nephrin、podocin 蛋白及 mRNA 表达均减少(P<0.01);洛沙坦干预治疗后 nephrin、podocin 表达上调(P<0.01),足细胞病变改善,尿蛋白排泄减少(P<0.01)。结论洛沙坦能通过上调nephrin、podocin 表达、改善足细胞超微结构,减少 DN 大鼠蛋白尿,保护肾功能。
Objective To investigate the effects of losartan on the ultrastructure of podocytes and the expressions of nephrin and podocin in diabetic nephropathy rats. Methods DN model rats were randomly divided into DN model group, intervention group and another group. Losartan 50 mg / (kg · d) was given to the intervention group and 24 h urinary protein The protein and mRNA expressions of nephrin and podocin in the renal cortex were detected by immunohistochemistry and RT-PCR. The ultrastructural changes of podocytes were detected by transmission electron microscopy. Results The 24 h urinary protein excretion increased (P <0.01), the number of podocytes decreased, the number of podocytes broadened, the expression of nephrin and podocin protein and mRNA decreased (P <0.01), while the expression of nephrin and podocin decreased after Losartan treatment (P <0.01), podocyte lesions improved, urinary protein excretion decreased (P <0.01). Conclusion Losartan can improve nephrin and podocin expression, improve podocyte ultrastructure, reduce proteinuria in DN rats and protect renal function.