骨化三醇对单侧输尿管梗阻大鼠肾小管上皮细胞转分化影响的研究

摘要

目的 观察幼年大鼠单侧输尿管梗阻(UUO)肾组织中α-肌动蛋白(α-SMA)、E-钙黏蛋白(E-Cad)、转化生长因子-β1(TGF-β1)、骨形态发生蛋白-7(BMP-7)mRNA的表达,探讨骨化三醇对肾小管上皮细胞转分化(EMT)干预效应及机制.方法 54只雄性SD大鼠随机分为3组:假手术组(A组)、UUO模型组(B组)及UUO模型干预组(C组)各18只,灌胃满3、7、14 d取肾.实时荧光定量聚合酶链反应(RT-PCR)法检测各组α-SMA、E-Cad、TGF-β1、BMP-7 mRNA表达水平.结果 与A组相比,B组E-Cad、BMP-7 mRNA表达明显下降(P＜0.01),α-SMA、TGF-β1mRNA表达显著增高(P＜0.01)；C组与B组相比,E-Cad、BMP-7 mRNA表达明显上调(P＜0.01),α-SMA、TGF-β1 mRNA表达明显下降(P＜0.0=1).结论 骨化三醇对UUO模型大鼠肾小管上皮细胞转分化有抑制作用,这种抑制作用可能与下调TGF-β1的表达及上调BMP-7的表达有关.%Objective To determine the effects and potential mechanisms of calcitriol on tubular epithelial myofibroblast transdifferentiation (EMT) in young rats with unilateral ureteral obstruction (UUO), based on the expression of renal tubulointerstitial α-smooth muscle actin (α-SMA), E-cadherin (E-Cad), transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7) mRNA. Methods Fifty-four male Sprague-Dawley rats were randomly allocated into Sham group (group A, n=18), UUO model group (group B, n=18) and UUO treatment group (group C, n= 18). The renal tissue was biopsied at days 3, 7 and 14 for subsequent assays of α-SMA, E-Cad, TGF-β1 and BMP-7 mRNA expression by using real-time fluorescence quantitative polymerase chain reaction (RT-PCR). Results Compared with group A, significantly attenuated E-Cad and BMP-7 mRNA expression yet markedly increased α-SMA and TGF-β1 mRNA was noted in group B (all P＜0.01). Group C was characterized by considerably up-regulated E-Cad and BMP-7 mRNA expression yet down-regulated expression of α-SMA and TGF-β1 mRNA when compared with group B (all P＜0.01). Conclusion The fact that calcitriol suppresses EMT in rats with UUO may be associated with down-regulation of TGF-β1 mRNA expression and up-regulated expression of BMP-7 mRNA.