|本期目录/Table of Contents|

[1]杜桂芳,董金珂,张 婷,等.Fyn 与小鼠肝纤维化模型中胆汁酸代谢组分的相关性研究[J].传染病信息,2018,04:326-330.
 DU Gui-fang,DONG Jin-ke,ZHANG Ting,et al.Correlation between Fyn and bile acid metabolism in liver fibrosis mice model[J].Infectious Disease Information,2018,04:326-330.
点击复制

Fyn 与小鼠肝纤维化模型中胆汁酸代谢组分的相关性研究(PDF)

《传染病信息》[ISSN:1007-8134/CN:11-3886/R]

期数:
2018年04期
页码:
326-330
栏目:
论 著
出版日期:
2018-08-30

文章信息/Info

Title:
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陆荫英洪智贤
 100039 北京,解放军第三〇二医院肝脏肿瘤诊 疗与研究中心(杜桂芳、张婷、杨新瑞、卢姗姗、曲建慧、 陆荫英),肝胆外科一中心(洪智贤);550004 贵阳,贵州医 科大学临床医学院传染病学 2016 级(董金珂)
Author(s):
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
关键词:
肝纤维化胆汁酸代谢组学Fyn
Keywords:
liver fibrosis bile acids metabonomics Fyn
分类号:
R657.3 
DOI:
10.3969/j.issn.1007-8134.2018.04.006
文献标识码:
A
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。 
Abstract:
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 of α-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) and β-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.     

参考文献/References


[1] Seki E, Schwabe RF. Hepatic inflammation and fibrosis: functional links and key pathways[J]. Hepatology, 2015, 61(3):1066-1079.
[2] Amathieu R, Triba MN, Goossens C, et al. Nuclear magnetic resonance based metabolomics and liver diseases: secent advances and future clinical applications[J]. World J Gastroenterol, 2016, 22(1):417-426.
[3] McPhail MJW, Shawcross DL, Lewis MR, et al. Multivariate metabotyping of plasma accurately predicts survival in patients with decompensated cirrhosis[J]. J Hepatol, 2016, 64(5):1058-1067.
[4] Masubuchi N, Nishiya T, Imaoka M, et al. Promising toxicological biomarkers for the diagnosis of liver injury types: bile acid metabolic profiles and oxidative stress marker as screening tools in drug development[J]. Chem Biol Interact, 2016, 255:74-82.
[5] Li T, Chiang JY. Bile acid signaling in liver metabolism and diseases[J]. J Lipids, 2012, 2012:754067.
[6] H.ussinger D, Reinehr R. Osmotic regulation of bile acid transport, apoptosis and proliferation in rat liver[J]. Cell Physiol Biochem, 2011, 28(6):1089-1098.
[7] H.ussinger D, Kurz AK, Wettstein M, et al. Involvement of integrins and Src in tauroursodeoxycholate-induced and swellinginduced choleresi[J]. Gastroenterology, 2003, 124(5):1476- 1487.
[8] Cantore M, Reinehr R, Sommerfeld A, et al. The Src family kinase Fyn mediates hyperosmolarity-induced Mrp2 and Bsep retrieval from canalicular membrane[J]. J Biol Chem, 2011, 286(52):45014-45029.
[9] Chiang JY. Bile acid metabolism and signaling[J]. Compr Physio, 2013, 3(3):1191-1212.
[10] Shlomai A, Halfon P, Goldiner I, et al. Serum bile acid levels as a predictor for the severity of liver fibrosis in patients with chronic hepatitis C[J]. J Viral Hepat, 2013, 20(2):95-102.
[11] Wang X, Xie G, Zhao A, et al. Serum bile acids are associated with pathological progression of hepatitis B-induced cirrhosis[J]. J Proteome Res, 2016, 15(4):1126-1134.
[12] Masubuchi N, Sugihara M, Sugita T, et al. Oxidative stress markers, secondary bile acids and sulfated bile acids classify the clinical liver injury type: promising diagnostic biomarkers for cholestasis [J]. Chem Biol Interact, 2016, 255:83-91.
[13] Zhang H, Wang X, Hu P, et al. Serum metabolomic characterization of liver fibrosis in rats and anti-fibrotic effects of Yin-Chen-Hao- Tang[J]. Molecules, 2016, 21(1):E126. (2018-01-22 收稿 2018-03-18 修回)

备注/Memo

备注/Memo:
[ 基金项目] 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) [ 作者单位] 100039 北京,解放军第三〇二医院肝脏肿瘤诊 疗与研究中心(杜桂芳、张婷、杨新瑞、卢姗姗、曲建慧、 陆荫英),肝胆外科一中心(洪智贤);550004 贵阳,贵州医 科大学临床医学院传染病学 2016 级(董金珂) [ 通信作者] 洪智贤,E-mail: zqyhzx@sina.com
更新日期/Last Update: 2018-09-08