1,25-二羟维生素D3通过调节NF-κB和TGF-β1/Smad通路减轻小鼠非酒精型脂肪性肝炎和肝纤维化

Effect of dihydroxyvitamin D3 in regulating NF-κB and TGF-β1/Smad pathway in mice of non-alcoholic steatohepatitis and liver fibrosis

目的:观察脂肪性肝炎肝纤维化小鼠肝组织NF-κB和TGF-β1/Smad通路的变化以及1,25-二羟维生素D3对其干预作用。方法:将32只C57BL/6J小鼠随机分为空白对照组、蛋氨酸胆碱缺乏(MCD)组、VitD3处理组和hemin处理组。通过饲喂蛋氨酸-胆碱缺乏的食物8周诱导脂肪性肝炎和肝纤维化。用ELISA法检测TGF-β1的变化,用real-time PCR和Western blot方法检测NF-κB和Smad通路中关键分子表达的变化。结果:1,25-二羟维生素D3和hemin的处理减轻了肝脏的损伤,并且抑制了炎症和纤维化相关基因IKK-β、NF-κB、TGF-β1和Smad3的表达,上调了纤维化抑制基因Smad7的表达。结论:NF-κB和TGF-β1/Smad通路参与了非酒精型脂肪性肝炎和肝纤维化的发展,1,25-二羟维生素D3能够通过调节NF-κB和TGF-β1/Smad信号通路减轻肝损伤。

Objective:To investigate the effect of dihydroxyvitamin D3 in regulating NF-κB and TGF-β1/Smad pathway in mice of non-alcoholic steatohepatitis and liver fibrosis.Methods:Thirty-two C57BL/6Jmice fed with methionine-choline deficient(MCD)diet for 8weeks were randomly divided into4groups:normal control group,MCD group,VitD3 group and hemin group.TGF-β1were detected by ELISA and the key molecules expressed in NF-κB and TGF-β1/Smad pathway were measured by realtime PCR and Western blot.Results:Administration of dihydroxyvitamin D3 and hemin can significantly ameliorate mice liver injury by inhibiting the expression of IKK-β,NF-κB,TGF-β1and Smad3 and up-regulating the expression of Smad7.Conclusion:NF-κB and TGF-β1/Smad pathway plays an important role in non-alcoholic steatohepatitis and liver fibrosis and dihydroxyvitamin D3 could attenuate the liver injury by regulating NF-κB and TGF-β1/Smad pathway.