Fyn与小鼠肝纤维化模型中胆汁酸代谢组分的相关性研究  

Correlation between Fyn and bile acid metabolism in liver fibrosis mice model

作　　者：杜桂芳 董金珂 张婷 杨新瑞 卢姗姗 曲建慧[1] 陆荫英[1] 洪智贤[3] DU Gui-fang;DONG Jin-ke;ZHANG Ting;YANG Xin-rui;LU Shan-shan;QU Jian-hui;LU Yin-ying;HONG Zhi-xian(Comprehensive Liver Cancer Center,302 Military Hospital of China,Beijing 100039,China)

机构地区：[1]解放军第三〇二医院肝脏肿瘤诊疗与研究中心,北京100039 [2]贵州医科大学临床医学院 [3]解放军第三〇二医院肝胆外科一中心,北京100039

出　　处：《传染病信息》2018年第4期326-330,共5页Infectious Disease Information

基　　金：国家自然科学基金面上项目(81470865,81672467);中国肝炎防治基金会王宝恩肝纤维化研究基金(CFHPC20151025)

摘　　要：目的探讨四氯化碳诱导的小鼠肝纤维化模型中胆汁酸(bile acids,BAs)代谢的改变,并初步探索分子机制。方法选取6周龄的C57BL/6小鼠,用四氯化碳诱导6周为肝纤维化模型(肝纤维化组),正常饲养小鼠6周作为对照(健康组)。对2组小鼠肝脏进行病理评估和血清学检测,利用液相色谱与质谱联用技术检测血清中BAs各组分的含量,利用Western Blot检测肝组织中α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)和Fyn的表达量。结果四氯化碳诱导形成小鼠肝纤维化模型后,小鼠血清中BAs代谢各组分普遍升高,其中肝纤维化组中鹅去氧胆酸(chenodeoxycholic acid,CDCA)、去氧胆酸(deoxycholic acid,DCA)、牛磺-β-鼠胆酸(tauro-β-muricholic,T-βMCA)、熊去氧胆酸(ursodeoxycholic acid,UDCA)、α-鼠胆酸(α-muricholic acid,α-MCA)、β-鼠胆酸(β-muricholic acid,β-MCA)相比健康组均显著升高,Fyn的表达量也显著升高并且与UDCA、DCA、牛磺熊去氧胆酸(tauroursodeoxycholic acid,TCDCA)呈正相关的关系。结论本研究明确了四氯化碳诱导的小鼠肝纤维化模型中BAs各组分的改变,并揭示Fyn对BAs的合成和转运可能起重要调控作用,进而影响肝纤维化的形成。Objectives To investigate the changes of bile acids(BAs)metabolism in CCl4 induced liver fibrosis mice and primarily explore the molecular mechanism.Methods The 6-week-old C57BL/6 mice were divided into liver fibrosis group(liver fibrosis mice model induced by CCl4 for 6 weeks)and control group(normal mice fed for 6 weeks).Pathological assessment and serological tests were performed to evaluate liver tissue in all mice.The component contents of BAs in serum were determined by liquid chromatograph-mass spectrometer.Levels ofα-smooth muscle actin(α-SMA)and Fyn expression in liver tissue were detected by Western Blot.Results After liver fibrosis mice model was induced by CCl4,all the components of BAs in mice serum were increased.Compared with control group,chenodeoxycholic acid(CDCA),deoxycholic acid(DCA),Tauro-β-muricholic(T-βMCA),ursodeoxycholic acid(UDCA),α-muricholic acid(α-MCA)andβ-muricholic acid(β-MCA)were significantly increased.The expression of Fyn in liver tissue of liver fibrosis group was also significantly higher than that of control group,and was positively correlated with UDCA,DCA and tauroursodeoxycholic acid(TCDCA).Conclusions In this study,the changes of bile acids component in liver fibrosis mice model induced by CCl4 are identified,and the results indicate that Fyn may play an important role in regulating the synthesis and transport of BAs,thus affecting the formation of liver fibrosis.

关 键 词：肝纤维化 胆汁酸 代谢组学 FYN 

分 类 号：R657.3[医药卫生—外科学]