活性维生素D_3通过抑制TRPC6表达发挥糖尿病肾病的保护作用  

Protective effect of vitamin D_3 on kidney in STZ-induced diabetic rats by inhibiting TRPC6 expression

作　　者：宋志霞[1] 郭银凤[1] 周敏[1] 张晓良[1] 

机构地区：[1]东南大学附属中大医院肾内科,江苏南京210009

出　　处：《东南大学学报（医学版）》2014年第6期683-690,共8页Journal of Southeast University(Medical Science Edition)

基　　金：国家自然科学基金资助项目(81370826);江苏省十二五医学重点人才项目(RC2011124);中央高校基本科研业务费专项资金资助项目(CXLX13-122)

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 every6 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.

关 键 词：活性维生素D3 糖尿病肾病 足细胞 瞬时受体电位阳离子通道蛋白6 大鼠 

分 类 号：R587.2[医药卫生—内分泌]