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牛磺胆酸促进肝硬化发展的机制

乐英彪 王昆华 邹雷

乐英彪,王昆华,邹雷. 牛磺胆酸促进肝硬化发展的机制[J]. 临床肝胆病杂志, 2021, 37(11): 2658-2662. DOI: 10.3969/j.issn.1001-5256.2021.11.037
引用本文: 乐英彪,王昆华,邹雷. 牛磺胆酸促进肝硬化发展的机制[J]. 临床肝胆病杂志, 2021, 37(11): 2658-2662. DOI: 10.3969/j.issn.1001-5256.2021.11.037
YUE YB, WANG KH, ZOU L. Mechanism of taurocholic acid in promoting the progression of liver cirrhosis[J]. J Clin Hepatol, 2021, 37(11): 2658-2662. DOI: 10.3969/j.issn.1001-5256.2021.11.037
Citation: YUE YB, WANG KH, ZOU L. Mechanism of taurocholic acid in promoting the progression of liver cirrhosis[J]. J Clin Hepatol, 2021, 37(11): 2658-2662. DOI: 10.3969/j.issn.1001-5256.2021.11.037

牛磺胆酸促进肝硬化发展的机制

DOI: 10.3969/j.issn.1001-5256.2021.11.037
基金项目: 

国家自然科学基金 81870458

云南省科技厅项目 2018DH006

云南省科技厅项目 ZX2019-03-03

云南省云岭学者项目 YLXL20170002

详细信息
    通讯作者:

    邹雷,zl_8082@126.com

  • 中图分类号: R575.2

Mechanism of taurocholic acid in promoting the progression of liver cirrhosis

Research funding: 

The National Natural Science Foundation of China 81870458

Yunnan Engineering Technology Center of Digestive Disease 2018DH006

Yunnan Engineering Technology Center of Digestive Disease ZX2019-03-03

Yunling Scholar YLXL20170002

  • 摘要: 胆汁酸是胆汁的主要成分,其外分泌入肠道帮助脂质和脂溶性维生素的吸收,也可作为信号分子调节胆汁酸代谢,帮助维持肠道稳态。而肝硬化过程中伴有不同程度的胆汁淤积,造成胆管损伤,肝脏细胞暴露于高水平胆汁酸会加速肝硬化进展从而形成恶性循环。在这些异常升高的胆汁酸中,以牛磺胆酸(TCA)水平升高最为显著,提示TCA在肝硬化过程中可能发挥重要作用。而目前对于TCA在肝硬化中的作用机制的研究相对较少,现有国内外相关研究表明,高水平TCA(≥50 μmol/L)可以通过作用于肝脏细胞(肝星状细胞、肝细胞、肝祖细胞、胆管上皮细胞)从而促进肝硬化进展。探讨了TCA促进肝硬化的详细机制,提示TCA具有作为肝硬化生物标志物与治疗靶点的临床潜力。

     

  • 图  1  TCA的合成示意图

    注:C1,7α-羟基-4-胆甾烯-3-酮;C2,7α,12α-羟基-4-胆甾烯-3-酮;C3,5β-胆甾烷-3α,7α,12α-三醇;CYP7A1,胆固醇7α-羟化酶;HSD3B7,3β-羟基-Δ5-C27-类固醇脱氢酶;CYP8B1,甾醇12α-羟化酶;AKR1D1,Δ4-3-氧类固醇-5β还原酶;AKR1C4,3α-羟基类固醇脱氢酶;CYP27A1,甾醇27-羟化酶;THCA,3α,7α,12α-三羟基胆甾酸;BACS,胆脂酰CoA合成酶;VLCS,超长链脂酰CoA合成酶;AMACR,α-甲基酰基辅酶A消旋酶;DBP,D-双功能蛋白;SCPx,甾醇载体蛋白x;BAAT,氨基酸N-酰基转移酶;ASBT,钠依赖回肠尖端胆汁转运体;NTCP,牛磺胆酸钠转运蛋白;OATP,有机阴离子转运蛋白。

    图  2  TCA促纤维化作用

    注:Erk1/2,细胞外调节蛋白激酶;EGR-1,早期生长反应蛋白-1。

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  • 收稿日期:  2021-04-06
  • 录用日期:  2021-05-08
  • 出版日期:  2021-11-20
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