活性维生素D_3对单侧输尿管结扎大鼠肾间质转化生长因子-β/Smads信号轴核酸表达的影响  

Effects of 1,25-dihydroxy vitamin D_3 on TGF-β/Smads signaling axis mRNA expression in rats with renal interstitial obstruction

作　　者：李素仙[1] 马宏[1] 王凤娇[1] 潘丽丽[1] 李伟[1] 王成礼[1] 

机构地区：[1]山西医科大学第一临床医学院儿科,太原030001

出　　处：《中国药物与临床》2013年第3期294-297,共4页Chinese Remedies & Clinics

基　　金：山西高校科技研究开发基金(2003103)

摘　　要：目的研究幼年大鼠单侧输尿管结扎(UUO)模型中,转化生长因子(TGF)-β/Smads信号通路中TGF-β1、Smad3、Smad7mRNA表达趋势及相关性,探讨活性维生素D3对肾脏保护作用的可能机制。方法 3～4周龄幼年SD雄性大鼠54只,随机均分为3组,假手术组、UUO模型组、UUO模型干预组,模型组和干预组行左侧输尿管结扎术,干预组给予0.1μg·kg-1·d-1活性维生素D3灌胃,灌胃满3、7、14d后杀鼠取左肾,采用实时荧光定量-聚合酶链反应(RT-PCR)法检测各组TGF-β1、Smad3、Smad7mRNA表达水平。结果模型组TGF-β1、Smad3的mRNA表达均明显高于假手术组(P<0.01),Smad7的表达低于假手术组(P<0.01);活性维生素D3干预组TGF-β1、Smad3的mRNA表达明显低于模型组(P<0.01),但仍强于假手术组(P<0.01);Smad7的表达则明显强于模型组(P<0.01),低于假手术组(P<0.01);TGF-β1、Smad3mRNA的表达水平与Smad7mRNA的表达呈负相关。结论在幼鼠肾小管间质损伤过程中,TGF-β/Smads信号通路参与了其发生发展,其中TGF-β1、Smad3起促进作用,Smad7起抑制作用。活性维生素D3可能通过下调Smad3的表达,上调Smad7的表达,减少TGF-β1的产生而起保护作用。Objective To investigate the expression and correlation of transforming growth factor-β1 （TGF-β1）, Smad3 and SmadT, the markers of TGF-131/Smads signaling pathway, and to determine the potential renal protective mechanisms of 1,25-dihydroxyvitamin D3 in young rats with unilateral ureteral obstruction （UUO）. Methods A total of 54 male SD rats aged 3 to 4 weeks were randomly assigned to Sham operation, model group and 1,25-dihydroxyvita- min D3 treatment group, in the latter two of which the left urethral ligation was performed. In addition, rats in treat- ment group received 1,25-dihydroxyvitamin D3 intragastric feeding （0.1 pLg. kg-1.d-j）. The rats were sacrificed at days 3, 7 and 14 for extraction of the left kidney. Real-time fluorescence quantitative polymerase chain reaction （RT-PCR） was employed to determine the expression of TGF-β1 mRNA, Smad3 mRNA and Smad7 mRNA. Results The model group yielded marked expression of TGF-β1 mRNA and Smad3 mRNA yet attenuated Smad7 expression compared with Sham group （all P〈0.01）. In 1,25-dihydroxyvitamin Dj treatment group, the expression of TGF-β1 and Smad3 mRNA was suppressed when compared with that of model group, but not control group （both P〈O.01）. The Smad7 ex- pression was most considerable in Sham group, followed by treatment group and model group （both P〈0.01）. Further- more, the levels of TGF-β1 and Smad3 mRNA expression were negatively correlated with Smad7 mRNA. Conclusion TGF-lS/Smads signaling pathway plays a critical role in the pathogenesis of renal interstitial injury in young rats, which was promoted by TGF-~1 and Smad3 yet retarded by Smad7. The protection of the 1,25-dihydroxyvitamin D3 to renal interstitial injury may partly be attribute to the down-regulated expression of Smad3 and production of TGF-β1 and up-regulation of Smad7.

关 键 词：胆骨化醇 转化生长因子-β1 肾间质纤维化 单侧输尿管梗阻 SMAD 

分 类 号：R363[医药卫生—病理学]