[1]张艳培 梁 健 邓 鑫 梁明坤 张冰冰 徐粤娟.浅析肝纤维化发生机制[J].大众科技,2021,23(2):40-44.
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浅析肝纤维化发生机制()
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《大众科技》[ISSN:1008-1151/CN:45-1235/N]

卷:
23
期数:
2021年2
页码:
40-44
栏目:
医药与卫生
出版日期:
2021-02-20

文章信息/Info

Title:
A Brief Analysis of the Pathogenesis of Liver Fibrosis
作者:
张艳培 1 梁 健 2 邓 鑫 1 梁明坤 3 张冰冰 1 徐粤娟 1
（1.广西中医药大学研究生院，广西 南宁 530000； 2.广西大学医学院，广西 南宁 530000； 3.广西中医药大学附属瑞康医院，广西 南宁 530000）
关键词:
肝纤维化; 肝星状细胞; 信号通路; 细胞凋亡
Keywords:
liver fibrosis;  hepatic stellate cells;  signal pathway;  apoptosis
文献标志码:
A
摘要:
肝纤维化是各种原因肝损伤后引起的肝脏复杂病理变化，国内外近年来研究表明，如果积极干预，尤其是在早 期介入阻断肝纤维化的进展，甚至可以在一定程度上逆转肝纤维化，因此明确肝纤维化的诱发因素、发展机制及其可逆指标的 检测对治疗慢性肝病肝纤维化即预防肝纤维化进展为肝硬化有一定的意义。但是目前肝纤维化的发生进展的机制仍未有较为明 确的定论。文章通过研究近年来阐述肝纤维化发生、发展机制相关的文献，并对文献中有证据支持的肝纤维化发展过程中的相 关机制做总结归纳，为肝纤维化的治疗及验证肝纤维化相关实验设计提供思路及理论支持。
Abstract:
Liver fibrosis is a complex pathological change of liver caused by various causes of liver injury. In recent years, studies at home and abroad have shown that active intervention, especially early intervention to block the progress of liver fibrosis, can even reverse liver fibrosis to a certain extent. Therefore, it is important to clarify the inducing factors, development mechanism and reversible indexes of liver fibrosis in the treatment of chronic liver disease, that is to say, it has certain significance to prevent liver fibrosis from developing into cirrhosis. However, the mechanism of the development of liver fibrosis has not been clearly defined. In this paper, through the study of the literature related to the occurrence and development mechanism of liver fibrosis in recent years, we summarize the relevant mechanisms in the development process of liver fibrosis supported by evidence in the literature, so as to provide ideological and theoretical support for the treatment and verification of liver fibrosis related experimental design.

参考文献/References:

[1] Tsuchida T, Friedman S L. Mechanisms of hepatic stellate cell activation[J]. Nature Reviews Gastroenterology and Hepatology, 2017(14): 397-411. [2] 夏家露，严醒，刘亚如，等. SOCS3 对四氯化碳诱导的 小鼠肝纤维化进展和逆转的影响及机制研究[J]. 中国药 理学通报，2017，33(9): 1215-1221. [3] Panday A, Sahoo M K, Osorio D, et al. NADPH oxidases: an overview from structure to innate immunity-associated pathologies[J]. Cellular and Molecular Immunology Volume, 2015, 12(1): 5-23. [4] Wang C, Li Y, Li H, et al. Disruption of FGF signaling ameliorates inflammatory response in hepatic stellate - 44 - cells[J]. Frontiers in Cell and Developmental Biology, 2020(8): 601. [5] 屈豫花，刘仁贵，秦燕. 胃饥饿素在缺血再灌注损伤介 导肝纤维化中对基质金属蛋白酶/基质金属蛋白酶组织 抑制因子的调控[J]. 实用医学杂志，2020，36(17): 2353-2359. [6] Marrone G, Shah V H, Gracia-Sancho J. Sinusoidal communication in liver fibrosis and regeneration[J]. Journal of Hepatology, 2016, 65(3): 608-617. [7] 朱立娜，张旭谱，杨耀娴，等. 血清白介素-1、白介素-6、 肿瘤坏死因子-α 与慢性肝病的相关性研究[J]. 包头医学 院学报，2008(4): 341-343. [8] 汪艳. 肿瘤坏死因子、白细胞介素-17 参与炎性小体介导 的肝脏无菌性炎症和纤维化发生[J]. 肝脏，2018，23(5): 377-378. [9] Xia Y, Yu B, Ma C, et al. Yu Gan Long reduces rat liver fibrosis by blocking TGF-β1/Smad pathway and modulating the immunity[J]. Biomedicine and Pharmacotherapy, 2018 (106): 1332-1338. [10] 刘立新，张骞骞，等. 1IGFBP2、IGFBP6 在 TGF-β1 活 化的肝星状细胞中表达[J]. 中国病理生理杂志，2008， 24(12): 2481-2483. [11] 周凯华，石兴民. 不同程度肝纤维化患者 IGF-2 及 IGFBP-2 与 MMPs 家族相关性分析[J]. 陕西医学杂志， 2015，44(8): 972-974. [12] 任俊杰. 小鼠肝纤维化形成中 IGFBPrP1对MMPs/TIMPs 平衡的调节及其机制研究[D]. 晋中: 山西医科大学， 2018. [13] 王艳景，谷征，李圆圆. MicroRNA-29b 对肝纤维化及肝 星状细胞增殖、凋亡的影响[J]. 中国现代医学杂志， 2018，28(32): 18-24. [14] 田淑霞，阮君，肖铁钢，等. 成纤维细胞生长因子 21 在 酒精性肝纤维化形成中的作用[J]. 肝脏，2017，22(12): 1098-1102. [15] 王大秀，韩继武. 成纤维细胞生长因子 21 对小鼠肝纤维 化的作用及其机制[J]. 临床肝胆病杂志，2018，34(6): 1215-1219. [16] Xu P, Zhang Y, Liu Y, et al. Fibroblast growth factor 21 attenuates hepatic fibrogenesis through TGF-β/smad2/3 and NF-κB signaling pathways[J]. Toxicology and Applied Pharmacology, 2016(290): 43-53. [17] 王超秀，陈炘，刘发彬，等. 血清凝血酶原活动度及相 关因素对重度慢性肝炎肝纤维化患者预后的影响分析 [J]. 川北医学院学报，2019，34(3): 441-444. [18] Dhar A, Sadiq F, Anstee Q M, et al. Thrombin and factor Xa link the coagulation system with liver fibrosis[J]. BMC Gastroenterology, 2018, 18(1): 60. [19] 陈元淦，张超，李方跃，等. PTP1B 及瘦素信号通路在奥 曲肽抗大鼠肝纤维化中的作用[J]. 安徽医科大学学报， 2016，51(4): 501-505. [20] 周光耀，林巍，金玲湘，等. 瘦素对大鼠肝纤维化及胞 外信号调节激酶通路的影响[J]. 国际流行病学传染病学 杂志，2014，41(2): 77-81. [21] Martin I V, Borkham-Kamphorst E, Zok S. Plateletderived growth factor (PDGF)-C neutralization reveals differential roles of PDGF receptors in liver and kidney fibrosis[J]. American Journal of Pathology, 2013, 182(1): 107-117 [22] Pinzani M, Marra F. cytokine receptors and signaling in hepatic stellate cells[J]. Seminars in Liver Disease, 2001, 21(3): 397-416. [23] 李源源，高莹，曹蕾，等. 血清 PDGF、ApoB/ApoA1 与 原发性胆汁性肝硬化的相关性分析[J]. 肝脏，2019， 24(11): 1248-1250. [24] 吴斌，王蓉，李胜男，等. 秦皮素通过调节 JAK1/STAT3 信号通路抑制肝纤维化[J]. 中南药学，2019，17(3): 420-425. [25] 岳彩飞，洪汝涛，徐德祥，等. 褪黑素对 PDGF 诱导的 肝星状细胞中 JAK2/STAT3 信号通路的影响[J]. 中国药 理学通报，2020，36(3): 403-407. [26] Niba E T, Nagaya H, Kanno T, et al. Crosstalk between PI3 kinase/PDK1/Akt/Rac1 and Ras/Raf/MEK/ERK pathways downstream PDGF receptor[J]. Cellular Physiology and Biochemistry, 2013, 31(6): 905-913. [27] Li H G, You P T, Xia Y, et al. Yu Gan Long Ameliorates Hepatic Fibrosis by Inhibiting PI3K/AKT, Ras/ERK and JAK1/STAT3 Signaling Pathways in CCl4-induced Liver Fibrosis Rats[J]. Current Medical Science, 2020, 40(3): 539-547. [28] Swiderska-Syn M, Xie G, Michelotti G A, et al. Hedgehog regulates yes-associated protein 1 in regenerating mouse liver[J]. Hepatolog, 2016, 64(1): 232-244. [29] 黄大伟，陆定波，高翔，等. 抗纤软肝颗粒调控 Hedgehog 通路核转录因子 Gli1 抑制肝星状细胞活化的研究[J]. 中 西医结合肝病杂志，2017，27(1): 37-39. [30] Feng J, Wang C, Liu T, et al. Procyanidin B2 inhibits the activation of hepatic stellate cells and angiogenesis via the Hedgehog pathway during liver fibrosis[J]. Journal Of Cellular and Molecular Medicine, 2019(9): 6479-6493. [31] Du K, Hyun J, Premont R T, et al. Hedgehog-YAP signaling pathway regulates glutaminolysis to control activation of hepatic stellate cells[J]. Gastroenterology, 2018, 154(5): 1465-1479. [32] Lee J H, Jang E J, Seo H L, et al. Sauchinone attenuates liver fibrosis and hepatic stellate cell activation through TGF-β/Smad signaling pathway[J]. Chemico-Biological Interactions, 2014(224): 58-67. [33] Wang Z C, Yang S, Huang J J, et al. Effect of bone marrow mesenchymal stem cells on the Smad expression of hepatic fibrosis rats[J]. Asian Pacific Journal of Tropical Medicine, 2014, 7(4): 321-324. [34] Xie H, Xie D, Zhang J, et al. ROS/NF-κB signaling pathway-mediated transcriptional activation of TRIM37 promotes HBV-associated hepatic fibrosis[J]. Molecular Therapy-Nucleic Acids, 2020(22): 114-123. [35] Moreno-Alvarez P, Sosa-Garrocho M, Briones-Or-Ta M A, et al. Angiotensin II increases mRNA levels of all TGF-betaisoforms in quiescent and activated rat hepatic stellate cells[J]. Cell Biology International, 2010, 34(10): 969-978. [36] Li Y S, Ni S Y, Meng Y, et al. Angiotensin II facilitates fibrogeniceffect of TGF-β1 through enhancing the down-regulation ofBAMBI caused by LPS: a new pro-fibrotic mechanism of angioten-sin II[J]. PLoS One, 2013, 8(10): e76289. [37] 曹海霞，颜士岩，汪保灿，等. 血管紧张素Ⅱ靶向调控 血小板源性生长因子信号通路促进肝纤维化的形成[J]. 实用医学杂志，2016，32(7): 1070-1073. [38] Donohoe F, Wilkinson M, Baxter E, et al. Mitogen-activated protein kinase (MAPK) and obesity-related cancer[J]. International Journal of Molecular Sciences, 2020, 21(4): 1241. [39] Li, X, Wang X, Han C, et al. Astragaloside IV suppresses collagen production of activated hepatic stellate cells via oxidative stress-mediated p38 MAPK pathway[J]. Free Radical Biology and Medicine, 2013(60): 168-176. [40] Qiang H, Lin Y, Zhang X, et al. Differential expression genes analyzed by cDNA array in the regulation of rat hepatic fibrogenesis[J]. Liver International, 2006(9): 1126-1137. [41] Schwabe R F, Schnabl B, Kweon Y O, et al. CD40 activates NF-kappa B and c-Jun N-terminal kinase and enhanceschemokine secretion on activated human hepatic stellate cells[J]. Journal of Immunology, 2001, 166(11): 6812-6819. [42] Campbell J S, Argast G M, Yuen S Y, et al. Inactivation of p38 MAPK during liver regeneration[J]. International Journal of Biochemistry and Cell Biology, 2011(2): 180-188. [43] 陈毅雄，翁志宏，祁丹，等. 调控 Notch 信号对肝星状细 胞活化的影响[J]. 中华肝脏病杂志，2012，20(9): 677-682. [44] 吴鹏，王亚东，方颖，等. 肝豆灵抑制 Notch 信号通路干 预铜负荷致肝纤维化大鼠肝脏上皮-间质转化[J]. 安徽中 医药大学学报，2018，37(6): 79-84. [45] 赵文冰，孔心涓，姜英俊，等. Notch 通路及 Snail 在大 鼠肝纤维化发生发展中的作用[J]. 齐鲁医学杂志，2014， 29(1): 22-25.

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备注/Memo

备注/Memo:
【收稿日期】2020-12-05 【基金项目】广西中医药大学校级一般硕士研究生创新项目（YCSY20190018）。 【作者简介】张艳培（1989－），男，河南舞钢人，广西中医药大学在读硕士研究生，研究方向为中西医结合防治消化 系统疾病。 【通信作者】梁健（1963－），男，广西南平人，广西大学医学院教授，主任医师，博士生导师，博士，研究方向为消 化系统疾病及肿瘤的临床和基础研究。
更新日期/Last Update: 2021-05-19