酒精对HBV转基因小鼠肝脏的损伤作用及其机制

The effect and mechanism of alcohol on liver injury in hepatitis B virus transgenic mice

目的探讨在肝损伤早期酒精和HBV协同作用的分子机制。方法20只HBV转基因小鼠和20只普通小鼠随机分为4组:转基因小鼠酒精组(alcohol-fed Tg mice)和普通小鼠酒精组(alcohol-fed Wt mice),以白酒灌胃;转基因小鼠对照组(control Tg mice)和普通小鼠对照组(control Wtmice),以生理盐水灌胃。连续处理10wk后检测各组小鼠血清ALT、AST水平,肝组织转化生长因子-β1(TGF-β1)、Smad3、Smad7、结缔组织生长因子(CTGF)mRNA表达水平及TGF-β1、CTGF、α-平滑肌肌动蛋白(α-SMA)蛋白表达水平。结果酒精可升高转基因小鼠血清ALT、AST水平,诱发其肝脏病理损伤,但纤维化不明显;肝组织TGF-β1、Smad3、Smad7、CTGF mRNA及TGF-β1、CTGF、α-SMA蛋白表达增加。结论酒精和HBV对肝损伤协同作用的机制可能与TGF-β1、Smad3、CTGF、α-SMA表达增加以及TGF-β1/Smads通路信号分子表达比例失调有关。

Aim To investigate the synergistic effects and possible molecular mechanism of hepatitis B virus（HBV）and alcohol on liver injury in HBV transgenic mice（HBV-Tg mice）.Methods 20 HBV-Tg mice and 20 wild-type mice were randomly divided into 4 groups：alcohol-fed Tg mice and alcohol-fed Wt mice,and they were given intragastric administration with alcohol.Control Tg mice and control Wt mice received intragastric administration with saline.All groups were rasied for 10 weeks.The levels of ALT and AST in serum,the degree of inflammation,the degree of fibrosis,the mRNA expression of TGF-β1,Smad3,Smad7,CTGF and the protein expression of TGF-β1,CTGF,α-SMA in liver tissue were detected.Results The serumlevel of ALT and AST,the mRNA expression of TGF-β1,Smad3,Smad7,CTGF and the protein expression of TGF-β1,CTGF,α-SMA in liver all increased markedly in alcohol-fed Tg mice.Alcohol consumption induced hepatocyte steatosis and hepatic inflammation in alcohol-fed Tg mice,but the change of liver fibrosis was not remarkable.Conclusion HBV and alcohol have synergistic effects on early liver injury,possibly by enhancing the expression of TGF-β1,Smad3,CTGF,α-SMA and inducing unbalanced expression of Smads.