胆汁酸代谢在肝硬化并发症中的研究进展

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (1): 103-107.

胆汁酸代谢在肝硬化并发症中的研究进展

张雪梅¹, 李俊峰^1*, 毛小荣^2*

兰州大学 1.第一临床医学院; 2.第一医院感染科, 甘肃兰州 730000

收稿日期:2019-12-05 修回日期:2020-03-26 出版日期:2021-01-05 发布日期:2020-12-30
通讯作者: ^*junfenglee@126.com;mxr2013@126.com
基金资助:
国家自然科学基金(81800528);甘肃省卫生行业科研计划(GSWSKY2018-24);甘肃省高等学校科学研究(2018B-009); 兰州大学第一医院院内基金(ldyyyn2017-17);兰州市城关区科研专项(2018SHFZ0023)

Research progress of bile acid metabolism in complications of liver cirrhosis

ZHANG Xue-mei¹, LI Jun-feng^1*, MAO Xiao-rong^2*

1. the First Clinical Medical College; 2. Department of Infection, the First Hospital, Lanzhou University, Lanzhou 730000, China

Received:2019-12-05 Revised:2020-03-26 Online:2021-01-05 Published:2020-12-30
Contact: ^*junfenglee@126.com;mxr2013@126.com

摘要/Abstract

摘要： 胆汁酸在肝细胞内以胆固醇为原料合成,在脂肪和脂溶性维生素的吸收、转运、分配中发挥作用,还作为重要的信号分子,调节代谢与炎性反应。胆汁酸在体内的蓄积及胆汁酸相关受体的激活可以加重或减轻肝硬化并发症如肝性脑病、门静脉高压、腹膜炎的进程。

关键词: 胆汁酸, 肝性脑病, 门静脉高压, 腹膜炎

Abstract: Bile acids are synthesized from cholesterol in hepatocytes and play an important role in the absorption, transport and distribution of fat and fat soluble vitamins. They also act as important signal molecules to regulate metabolism and inflammatory response. The accumulation of bile acids in the body and the activation of bile acid related receptors can aggravate or alleviate the complications of liver cirrhosis such as hepatic encephalopathy, portal hypertension and peritonitis.

Key words: bile acid, hepatic encephalopathy, portal hypertension, peritonitis

中图分类号:

R512.6

张雪梅, 李俊峰, 毛小荣. 胆汁酸代谢在肝硬化并发症中的研究进展[J]. 基础医学与临床, 2021, 41(1): 103-107.

ZHANG Xue-mei, LI Jun-feng, MAO Xiao-rong. Research progress of bile acid metabolism in complications of liver cirrhosis[J]. Basic & Clinical Medicine, 2021, 41(1): 103-107.

参考文献

[1] Yang YM, Roh YS,Seki E. MafG a novel target of FXR that regulates bile acid homeostasis[J]. Gastroenterology,2015, 149: 1981-1983.
[2] Xu Y, Li F, Zalzala M, et al. Farnesoid X receptor activation increases reverse cholesterol transport by modulat-ing bile acid composition and cholesterol absorption in mice[J]. Hepatology, 2016, 64: 1072-1085.
[3] Pathak P, Xie C, Nichols RG, et al. Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabo-lism[J]. Hepatology, 2018, 68: 1574-1588.
[4] Schwabl P, Hambruch E, Seeland BA, et al. The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction[J]. J Hepatol, 2017, 66: 724-733.
[5] Shetty S,Boyer JL. Bile acid metabolism and T cell responses in cholangiopathy: not one-way traffic[J]. J Hepatol,2019, 71: 657-659.
[6] Guo C, Xie S, Chi Z, et al. Bile acids control inflammation and metabolic disorder through inhibition of NLRP3 inflammasome[J]. Immunity, 2016, 45: 802-816.
[7] Horvatits T, Drolz A, Roedl K, et al. Serum bile acids as marker for acute decompensation and acute-on-chronic liver failure in patients with non-cholestatic cirrhosis[J]. Liver Int,2017, 37: 224-231.
[8] Weiss N, Barbier Saint Hilaire P, Colsch B, et al. Cerebrospinal fluid metabolomics highlights dysregulation of energy metabolism in overt hepatic encephalopathy[J]. J Hepatol, 2016, 65: 1120-1130.
[9] Acharya C,Bajaj JS. Gut microbiota and complications of liver disease[J]. Gastroenterol Clin North Am,2017, 46: 155-169.
[10] Ahluwalia V, Betrapally NS, Hylemon PB, et al. Impaired gut-liver-brain axis in patients with cirrhosis[J]. Sci Rep, 2016, 6: 26800.doi:10.1038/srep26800.
[11] Bajaj JS,Khoruts A. Microbiota changes and intestinal microbiota transplantation in liver diseases and cirrhosis[J]. J Hepatol, 2020. doi:10.1016/j.jhep.2020.01.017.
[12] Bajaj JS, Heuman DM, Hylemon PB, et al. Altered profile of human gut microbiome is associated with cirrho-sis and its complications[J]. J Hepatol, 2014, 60: 940-947.
[13] Baffy G. Potential mechanisms linking gut microbiota and portal hypertension[J]. Liver Int, 2019, 39: 598-609.doi:10.1111/liv.13986.
[14] Ma C, Han M, Heinrich B, et al. Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells[J]. Science, 2018, 360.doi:10.1126/science.aan5931.
[15] Xie G, Wang X, Jiang R, et al. Dysregulated bile acid signaling contributes to the neurological impairment in murine models of acute and chronic liver failure[J]. EBioMedicine, 2018, 37: 294-306.
[16] Jia W, Rajani C, Kaddurah-Daouk R, et al. Expert insights: the potential role of the gut microbiome-bile acid-brain axis in the development and progression of Alzheimer's disease and hepatic encephalopathy[J]. Med Res Rev,2019. doi:10.1002/med.21653.
[17] McMillin M, Frampton G, Grant S, et al. Bile acid-mediated sphingosine-1-phosphate receptor 2 signaling pro-motes neuroinflammation during hepatic encephalopathy in mice[J]. Front Cell Neurosci, 2017, 11: 191.doi:10.3389/fncel.2017.00191.
[18] Villanueva C, Albillos A, Genescà J, et al. β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial[J]. The Lancet, 2019, 393: 1597-1608.
[19] Fiorucci S,Distrutti E. Targeting the transsulfuration-H₂S pathway by FXR and GPBAR1 ligands in the treatment of portal hypertension[J]. Pharmacol Res,2016, 111: 749-756.
[20] Mookerjee RP, Mehta G, Balasubramaniyan V, et al. Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension[J]. J Hepatol,2015, 62: 325-331.
[21] Xu W, Lu C, Zhang F, et al. Dihydroartemisinin counteracts fibrotic portal hypertension via farnesoid X receptor-dependent inhibition of hepatic stellate cell contraction[J]. FEBS J, 2017, 284: 114-133.
[22] Fiorucci S, Zampella A, Cirino G, et al. Decoding the vasoregulatory activities of bile acid-activated receptors in systemic and portal circulation: role of gaseous mediators[J]. Am J Physiol Heart Circ Physiol, 2017, 312: H21-H32.
[23] Li YT, Yu CB, Huang JR, et al. Pathogen profile and drug resistance analysis of spontaneous peritonitis in cirrhotic patients[J]. World J Gastroenterol, 2015, 21: 10409-10417.
[24] Sorribas M, Jakob MO, Yilmaz B, et al. FXR modulates the gut-vascular barrier by regulating the entry sites for bacterial translocation in experimental cirrhosis[J]. J Hepatol, 2019, 71: 1126-1140.
[25] Lachar J,Bajaj JS. Changes in the microbiome in cirrhosis and relationship to complications: hepatic encephalopathy, spontaneous bacterial peritonitis, and sepsis[J]. Semin Liver Dis, 2016, 36: 327-330.
[26] Chavez-Talavera O, Tailleux A, Lefebvre P, et al. Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease[J]. Gastroenterology, 2017, 152: 1679-1694.