中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

肝纤维化的分子基础与临床诊治现状

李妍 陆伦根

李妍, 陆伦根. 肝纤维化的分子基础与临床诊治现状[J]. 临床肝胆病杂志, 2018, 34(1): 12-15. DOI: 10.3969/j.issn.1001-5256.2018.01.001.
引用本文: 李妍, 陆伦根. 肝纤维化的分子基础与临床诊治现状[J]. 临床肝胆病杂志, 2018, 34(1): 12-15. DOI: 10.3969/j.issn.1001-5256.2018.01.001.
Li Yan, Lu LunGen. Molecular basis of hepatic fibrosis and current status of its diagnosis and treatment[J]. J Clin Hepatol, 2018, 34(1): 12-15. DOI: 10.3969/j.issn.1001-5256.2018.01.001.
Citation: Li Yan, Lu LunGen. Molecular basis of hepatic fibrosis and current status of its diagnosis and treatment[J]. J Clin Hepatol, 2018, 34(1): 12-15. DOI: 10.3969/j.issn.1001-5256.2018.01.001.

肝纤维化的分子基础与临床诊治现状

DOI: 10.3969/j.issn.1001-5256.2018.01.001
详细信息
  • 中图分类号: R575.2

Molecular basis of hepatic fibrosis and current status of its diagnosis and treatment

  • 摘要: 慢性肝损伤时,肝星状细胞与肝实质细胞、Kupffer细胞、肝窦内皮细胞等多种细胞相互作用,介导细胞外基质沉积与肝窦毛细血管化,启动肝纤维化进程,其本质是肝损伤后的修复反应。肝穿刺活组织检查技术是肝纤维化诊断的金标准,但有一定出血风险及死亡风险。无创性诊断肝纤维化的手段主要包括血清分子标志物、影像学诊断技术以及预测性统计模型等,但其尚不能完全替代肝穿刺活组织检查。目前,肝纤维化的治疗主要针对原发疾病、以肝星状细胞为靶点的药物研发、以细胞外基质合成/降解平衡为靶点的药物研发等方面。研究肝纤维化分子机制,为探索肝纤维化治疗提供了坚实的理论基础。

     

  • [1]FRIEDMAN SL.Hepatic stellate cells:protean, multifunctional, and enigmatic cells of the liver[J].Physiol Rev, 2008, 88 (1) :125-172.
    [2]FRIEDMAN SL.Mechanisms of hepatic fibrogenesis[J].Gastroenterology, 2008, 134 (6) :1655-1669.
    [3]DUFFIELD JS, FORBES SJ, CONSTANDINOU CM, et al.Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair[J].J Clin Invest, 2005, 115 (1) :56-65.
    [4]NOVO E, PAROLA M.The role of redox mechanisms in hepatic chronic wound healing and fibrogenesis[J].Fibrogenesis Tissue Repair, 2012, 5 (Suppl 1) :s4.
    [5]DUBUISSON L, DESMOULIERE A, DECOURT B, et al.Inhibition of rat liver fibrogenesis through noradrenergic antagonism[J].Hepatology, 2002, 35 (2) :325-331.
    [6]TIAN X, ZHAO C, GUO J, et al.Carvedilol attenuates the progression of hepatic fibrosis induced by bile duct ligation[J].Biomed Res Int, 2017, 2017:4612769.
    [7] ARAU'JO JU'NIOR RF, GARCIA VB, LEITAO RF, et al.Carvedilol improves inflammatory response, oxidative stress and fibrosis in the alcohol-induced liver injury in rats by regulating Kuppfer cells and hepatic stellate cells[J].PLo S One, 2016, 11 (2) :e0148868.
    [8]GRANT A, NEUBERGER J.Guidelines on the use of liver biopsy in clinical practice.British Society of Gastroenterology[J].Gut, 1999, 45 (Suppl 4) :iv1-iv11.
    [9]ROCKEY DC, CALDWELL SH, GOODMAN ZD, et al.Liver biopsy[J].Hepatology, 2009, 49 (3) :1017-1044.
    [10]SCHIAVON LDE L, NARCISO-SCHIAVON JL, de CARVALHO-FILHO RJ.Non-invasive diagnosis of liver fibrosis in chronic hepatitis C[J].World J Gastroenterol, 2014, 20 (11) :2854-2866.
    [11]JIN B.Extracellular matrix and liver diseases[J].World Chin J Dig, 2002, 10 (1) :63-64. (in Chinese) 金博.细胞外基质与肝脏肿瘤[J].世界华人消化杂志, 2002, 10 (1) :63-64.
    [12]NEVES LB, CATARINO RM, SILVA MR, et al.Increased serum levels of laminin in the experimental cirrhosis induced by carbon tetrachloride[J].Arq Gastroenterol, 2003, 40 (3) :173-176.
    [13]BECKER L, SALAMEH W, SFERRUZZA A, et al.Validation of hepascore, compared with simple indices of fibrosis, in patients with chronic hepatitis C virus infection in United States[J].Clin Gastroenterol Hepatol, 2009, 7 (6) :696-701.
    [14]DEGOS F, PEREZ P, ROCHE B, et al.Diagnostic accuracy of Fibro Scan and comparison to liver fibrosis biomarkers in chronic viral hepatitis:a multicenter prospective study (the FIBROSTIC study) [J].J Hepatol, 2010, 53 (6) :1013-1021.
    [15]ZHANG D, LI P, CHEN M, et al.Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease using acoustic radiation force impulse elastography[J].Abdom Imaging, 2015, 40 (4) :723-729.
    [16]ADAMS LA, GEORGE J, BUGIANESI E, et al.Complex noninvasive fibrosis models are more accurate than simple models in non-alcoholic fatty liver disease[J].J Gastroenterol Hepatol, 2011, 26 (10) :1536-1543.
    [17]SHAH AG, LYDECKER A, MURRAY K, et al.Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease[J].Clin Gastroenterol Hepatol, 2009, 7 (10) :1104-1112.
    [18]CALES P, VEILLON P, KONATEA, et al.Reproducibility of blood tests of liver fibrosis in clinical practice[J].Clin Biochem, 2008, 41 (1-2) :10-18.
    [19]ROSSELLI M, Mac NAUGHTAN J, JALAN R, et al.Beyond scoring:a modern interpretation of disease progression in chronic liver disease[J].Gut, 2013, 62 (9) :1234-1241.
    [20]MANNE V, AKHTAR E, SAAB S.Cirrhosis regression in patients with viral Hepatitis B and C:a systematic review[J].J Clin Gastroenterol, 2014, 48 (9) :e76-e84.
    [21]MARCELLIN P, GANE E, BUTI M, et al.Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B:a 5-year open-label follow-up study[J].Lancet, 2013, 381 (9865) :468-475.
    [22]PAN CQ, CHAN S, TRINH H, et al.Similar efficacy and safety of tenofovir in Asians and non-Asians with chronic hepatitis B[J].World J Gastroenterol, 2015, 21 (18) :5524-5531.
    [23]TSAI NC, MARCELLIN P, BUTI M, et al.Viral suppression and cirrhosis regression with tenofovir disoproxil fumarate in Asians with chronic hepatitis B[J].Dig Dis Sci, 2015, 60 (1) :260-268.
    [24]D'AMBROSIO R, AGHEMO A, RUMI MG, et al.A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis[J].Hepatology, 2012, 56 (2) :532-543.
    [25]TROEGER JS, MEDERACKE I, GWAK GY, et al.Deactivation of hepatic stellate cells during liver fibrosis resolution in mice[J].Gastroenterology, 2012, 143 (4) :1073-1083.
    [26]HAO H, ZHANG D, SHI J, et al.Sorafenib induces autophagic cell death and apoptosis in hepatic stellate cell through the JNK and Akt signaling pathways[J].Anticancer Drugs, 2016, 27 (3) :192-203.
    [27]CALVARUSO V, MAIMONE S, GATT A, et al.Coagulation and fibrosis in chronic liver disease[J].Gut, 2008, 57 (12) :1722-1727.
    [28]ZHU L, CHENG M, LIU Y, et al.Thymosin-β4 inhibits proliferation and induces apoptosis of hepatic stellate cells through PI3K/AKT pathway[J].Oncotarget, 2017, 8 (40) :68847-68853.
    [29]PALUMBO-ZERR K, ZERR P, DISTLER A, et al.Orphan nuclear receptor NR4A1 regulates transforming growth factor-βsignaling and fibrosis[J].Nat Med, 2015, 21 (2) :150-158.
    [30]YANG D, LI L, QIAN S, et al.Evodiamine ameliorates liver fibrosis in rats via TGF-β1/Smad signaling pathway[J].J Nat Med, 2017.[Epub ahead of print]
    [31]TAKEMURA S, AZUMA H, OSADA-OKA M, et al.S-allylglutathione improves experimental liver fibrosis by regulating Kupffer cell activation in rats[J].Am J Physiol Gastrointest Liver Physiol, 2017.[Epub ahead of print]
    [32]XIE WF, LIN Y.Degradation of extracellular matrix and hepatic fibrosis therapy[J].World Chin J Dig, 2002, 10 (1) :61-63. (in Chinese) 谢渭芬, 林勇.细胞外基质降解与肝脏纤维化治疗[J].世界华人消化杂志, 2002, 10 (1) :61-63.
  • 期刊类型引用(18)

    1. 黄涛,王改莉,范京通,胡艳芳,袁伟,李振燕. 扶正化瘀胶囊对乙肝肝硬化患者肝硬化、肝功能影响. 临床军医杂志. 2023(04): 387-389 . 百度学术
    2. 徐静,严永敏,蔡梦洁. miR-373下调转化生长因子βⅡ型受体表达抑制肝星状细胞活化. 中国组织工程研究. 2022(05): 788-793 . 百度学术
    3. 李婷婷,肖政华,石以石则,谭芊任,崔峻松. 小柴胡汤联合恩替卡韦治疗慢性乙型病毒性肝炎的Meta分析. 中外医学研究. 2022(12): 9-14 . 百度学术
    4. 周怡驰,晏军,李玲,冉云,胡世平. 基于柴胡“推陈致新”与网络药理学探讨柴胡干预肝纤维化的分子机制. 中西医结合肝病杂志. 2022(07): 626-631 . 百度学术
    5. 李华忠,蔡笃雄,陈才利. 乙型肝炎肝纤维化患者血清miR-122与miR-17表达及其对肝纤维化的预测作用分析. 标记免疫分析与临床. 2021(09): 1542-1548 . 百度学术
    6. 吴芙蓉,宁丽娟,周冉. 小柴胡汤对化学性肝纤维化小鼠的保护作用. 中国临床药理学与治疗学. 2020(05): 481-488 . 百度学术
    7. 李硕熙,王炳予,杨磊,李丹丹,袁星星. 芪参汤通过PI3K/Akt/mTOR信号通路抗肝纤维化的机制研究. 海南医学院学报. 2020(12): 905-909+914 . 百度学术
    8. 陈炜璋,肖漪熙,李靖玉. 前瞻性护理在失代偿期肝硬化并发肝性脑病患者中的应用. 海南医学. 2020(14): 1899-1901 . 百度学术
    9. 郝芳芳,杨永寿,肖培云. 美洲大蠊抗肝纤维化活性部位的筛选. 中国临床药理学杂志. 2019(03): 241-244 . 百度学术
    10. 唐颖悦,李静,雷晓红,李春敏,曾民德,茅益民. CCl_4诱导肝纤维化小鼠模型中肝脏巨噬细胞及淋巴细胞亚群变化的初步分析. 肝脏. 2019(04): 377-381 . 百度学术
    11. 李天,吴岩,姬婷,金振晓. 叉头转录因子1/3在肝纤维化中的作用. 临床肝胆病杂志. 2019(08): 1842-1846 . 本站查看
    12. 廖庆英,关蓉,蒋吟啸,张雯雯,蒋坤秀,文建霞,魏士长,李浩田,马骁. 复方鳖甲软肝片联合恩替卡韦治疗慢性乙型病毒性肝炎伴肝纤维化的系统评价. 中国医院用药评价与分析. 2019(09): 1031-1038 . 百度学术
    13. 张艳芳,杨馥宁,车媛媛,黄晶. 血清YKL-40对肝纤维化分期诊断价值的Meta分析. 临床肝胆病杂志. 2018(09): 1896-1900 . 本站查看
    14. 杨新英,康富标,叶立红,戴二黑,孙殿兴. 慢性乙型肝炎及肝硬化患者血清高迁移率族蛋白B1水平变化及临床意义. 临床肝胆病杂志. 2018(09): 1901-1904 . 本站查看
    15. 何阳,宋立莹,彭向东,方伟进,王春江,邓珍珍,樊志强,刘世坤. 发酵虫草菌粉对DEN致大鼠肝损伤的保护作用及TGF-β1/Smads通路的影响. 中国临床药理学与治疗学. 2018(09): 974-982 . 百度学术
    16. 朱海燕,吴雄健,曾斌,谢志军. 神经生长因子及其低亲和力受体诱导肝星状细胞凋亡的初步研究. 中国当代医药. 2018(29): 8-10+14 . 百度学术
    17. 王诚,陈厚斌,马龙,田泽斌,郑直,周明雄. 肝动脉血流阻力指数对非酒精性脂肪性肝病患者进展期肝纤维化的评估价值. 临床肝胆病杂志. 2018(12): 2578-2581 . 本站查看
    18. 金学琴,黎伟华,李志梅,何生存,潘琳. 苦参素对肝纤维化大鼠肝脏转化生长因子-β1的调节作用. 畜牧与饲料科学. 2018(12): 13-16 . 百度学术

    其他类型引用(8)

  • 加载中
计量
  • 文章访问数:  2182
  • HTML全文浏览量:  11
  • PDF下载量:  626
  • 被引次数: 26
出版历程
  • 出版日期:  2018-01-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回