Objective To investigate the changes in podocyte ultrastructure and nephrin expression in rats with diabetic nephropathy(DN) ,and to observe the effect of candesartan on podocyte damage. Methods Thirty-six Sprague-Dawley rats were randomly divided into normal control group(group A),DN model group(group B),and candesartan treatment group (group C),with 12 rats in each group. DN was induced by intravenous injection of streptozotocin (30 mg · kg-1) and rats in group C were intragastricly given candesartan (5 mg · kg-1 · d-1) 1 week after induction of DN. Rats in group A and group B were given the same amount of normal saline. Blood glucose levels, body weight, 24-hour urinary protein excretion and endogenous creatinine clearance(Ccr) were measured at 4 and 7 weeks after treatment. Pathological changes in renal tissues were evaluated by HE staining and podocyte ultrastructure was observed using electron microscop. The expression of nephrin was detected by RT-PCR. Results Compared with group A, 24-hour urinary protein excretion and serum creatinine increased, Ccr decreased at 7 weeks, and nephrin expression reduced in group B(all P＜0. 05). Compared with group B, 24-hour urinary protein excretion,serum creatinine,foot process width and glomerular basement membrane thickness decreased,and Ccr and nephrin expression increased in group C (all P＜0.05). Conclusion DN patients have abnormal podocyte ultrastructure and nephrin expression. Candesartan can protect podocyte damage through up-regulating nephrin expression and improving podocyte ultrastructure.%目的 探讨糖尿病肾病(diabetic nephropathy,DN)大鼠足细胞超微结构及其相关分子nephrin表达的变化,以及坎地沙坦对其干预的影响,为DN的防治提供理论依据.方法 选择健康雄性SD大鼠36只,按随机数字表法分为A组(正常对照组)、B组(DN组)和C组(DN+坎地沙坦组),每组12只.B、C组尾静脉注射链脲佐菌素(30 mg·kg-1)制备DN大鼠模型,于DN模型成模1周后将3组大鼠分别在代谢笼中喂养,C组给予坎地沙坦5 mg·kg-1·d-1灌胃,A组及B组给予等量生理盐水灌胃.用药后第4周和第7周检测各组大鼠的血糖、体质量、24 h尿蛋白和内生肌酐清除率(Ccr),于第7周取肾组织行光学显微镜及电子显微镜观察肾脏病理改变、RTPCR法检测nephrin-mRNA表达.结果 与A组比较:B组24 h尿蛋白排泄增多(P＜0.05),Ccr在7周时下降(P＜0.05);肾组织内nephrin-mRNA表达下调(P＜0.05);肾组织足细胞足突宽度增加并出现融合,肾小球基底膜增厚.与B组比较:C组24 h尿蛋白排泄量降低(P＜0.05),Ccr升高(P＜0.05);肾组织内nephrin-mRNA表达增加(P＜0.05),足细胞足突宽度及肾小球基底膜厚度变小.结论 DN时存在足细胞分子nephrin表达异常和超微结构改变,坎地沙坦对肾脏的保护作用机制可能是通过增加nephrin表达、改善足细胞超微结构而实现.
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