活性维生素D<sub>3</sub>通过抑制TRPC6表达发挥糖尿病肾病的保护作用-东南大学学报医学版

活性维生素D₃通过抑制TRPC6表达发挥糖尿病肾病的保护作用

单位：东南大学附属中大医院肾内科, 江苏南京 210009

分类号：R587.2

出版年·卷·期（页码）：2014·33·第六期（683-690）

摘要：

目的: 探讨活性维生素D₃对链脲佐菌素(STZ)诱导糖尿病肾病(DN)大鼠的肾保护作用是否与抑制瞬时受体电位阳离子通道蛋白6(TRPC6)有关.方法: 30只雄性SD大鼠随机分为正常对照组(NC组)、DN组及DN加活性维生素D₃干预组(DN+VD组)3组各10只.造模成功后6、12、18周检测大鼠体重、24 h尿蛋白量;造模成功后18周末处死大鼠,检测血样及肾组织指标变化.结果: DN+VD组与DN组相比蛋白尿显著减少,肾脏病理损伤改善.DN组与NC组比较,Podocin、Nephrin蛋白表达量均明显降低(均P<0.05),Desmin和TRPC6蛋白表达量均显著升高(均P<0.05),活性维生素D₃干预后上述改变明显改善,差异有统计学意义.相关性分析显示: TRPC6与Podocin(r=-0.808,P<0.05)、Nephrin(r=-0.791,P<0.05)呈负相关,而与24 h尿蛋白(r=0.886,P<0.05)、Desmin(r=0.929,P<0.05)呈正相关.结论: 活性维生素D₃显著抑制STZ诱导的糖尿病大鼠肾脏损伤,其作用机制与调节足细胞TRPC6的表达有关.

Objective: To investigate the protective effect of vitamin D₃ on kidney in STZ-induced diabetic rats and its possible mechanism. Methods: Thirty male Spragam-Dawley rats were randomly divided into three groups: normal control(NC,n=10), diabetic nephropathy(DN,n=10),and DN treated with calcitriol(DN+VD group,n=10).DN model rats were established by intraperitoneal injections of STZ. Rats were sacrificed 18 w after treatment.Body weights were assessed and 24 h urine samples were collected in metabolic cages every 6 w starting at 3 d after STZ injection.All animals were sacrificed at 18 w after treatment.At the end of the experiment and prior to sacrifice,blood samples were collected for biochemical studies,and the kidneys were used for histological assessments, immunohistochemical staining and western blot. Results: Pre-treatment of rats with vitamin D₃ led to a significant attenuation proteinuric of rat experimental model of diabetes.This was associated with abrogation of disease associated induction of desmin and inhibition of TRPC6 expression.Vitamin D₃ teatment up-regulation the expression of Nephrin and Podocin.Significant positive correlation was observed between TRPC6 and 24 h urinary protein (r=0.886,P<0.05), Desmin(r=0.929,P<0.05) of podocyte injury maker. On the contrary, significant negative correlations were observed between TRPC6 protein and Nephrin expresion(r=-0.791,P<0.05) and Podocin(r=-0.808,P<0.05). Conclusion: Vitamin D₃ has protective effect on kidney in STZ-induced diabetic rats model, which might be related with the suppression of TRPC6 expresion.

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