中药抗肝纤维化实验研究进展
DOI: 10.3969/j.issn.1001-5256.2023.02.001
Advances in the experimental research on traditional Chinese medicine against liver fibrosis
-
摘要: 肝纤维化是由病毒性肝炎、酒精中毒等多种病因导致的慢性肝脏疾病的共同病理过程,可进展为肝硬化,乃至肝癌,严重威胁人类健康。中药在抑制肝纤维化进展和促进肝纤维化逆转方面有着“多成分-多靶点-多途径”的作用特点,具备独特的临床疗效。近年来,中药抗肝纤维化的实验研究取得了较大的进展,许多具有良好抗肝纤维化作用的中药复方和单味药及其有效成分被发现,并从细胞、分子水平等方面揭示了其潜在的作用机制。为进一步阐明中药抗肝纤维化实验研究进展,本文从中药抗肝纤维化实验动物模型、中药抗肝纤维化作用机理、从动物实验到临床试验的中药研究三方面,系统阐述了其近5年的研究进展,为科研人员及临床医师开展中药抗肝纤维化药物研发和应用提供参考。Abstract: Liver fibrosis is the common pathological process of chronic liver diseases caused by various etiologies such as viral hepatitis and alcoholism, and it can progress to liver cirrhosis and even liver cancer and seriously threatens human health. Traditional Chinese medicine (TCM) has the characteristics of multiple components, targets, and pathways in inhibiting the progression of liver fibrosis and promoting the reversal of liver fibrosis and thus has unique clinical efficacy. In recent years, great progress has been made in the experimental research on the anti-liver fibrosis potential of TCM, and related studies have found a variety of compound TCM prescriptions, single TCM medicine, and their effective constituents and revealed their potential mechanism of action from the cellular and molecular levels. In order to further clarify the advances in the experimental research on the anti-liver fibrosis potential of TCM, this article systematically reviews the research advances in the past five years from the aspects of experimental animal models for the anti-liver fibrosis potential of TCM, the mechanism of action of TCM in the treatment of liver fibrosis, and TCM research from animal experiments to clinical trials, so as to provide a reference for researchers and clinicians to develop and apply anti-liver fibrosis TCM drugs.
-
Key words:
- Liver Fibrosis /
- Traditional Chinese Medicine /
- Animal Model /
- Mechanism /
- Progress
-
表 1 肝毒素、非酒精性脂肪肝炎和胆道纤维化的肝纤维化模型诱导方法及特点[8]
Table 1. Induction methods and characteristics of hepatic fibrosis models of hepatotoxin, nonalcoholic steatohepatitis and biliary fibrosis[8]
项目 肝毒素导致的肝纤维化 非酒精性脂肪性肝炎肝纤维化 胆道纤维化 常用诱导方法 CCl4*、TAA*、DMN/DEN、酒精等 饮食:HFHCD*、MCD*
饮食+遗传修饰:foz/foz或db/db
小鼠+高脂饮食等手术:BDL*
饮食:DDC、CDE、ANIT
遗传修饰:Mdr2等造模时长 CCl4:6~12周
TAA:8~24周HFHCD:>24周
MCD: >12周BDL: 2~3周
Mdr2:>6周龄主要病理特点 间隔纤维化 网眼状纤维化 门静脉纤维化
洋葱皮样纤维化注:*代表最为常用的诱导方法。CCl4,四氯化碳;TAA,硫代乙酰胺;HFHCD,高脂高胆固醇饮食;MCD,蛋氨酸和胆碱缺乏饮食;BDL,胆管结扎术;CDE,缺乏胆碱的乙硫氨酸补充饮食;ANIT,α-异硫氰酸萘酯饮食;Mdr2,多药耐药相关蛋白2基因;DMN/DEN,二甲基亚硝胺和二乙基亚硝胺。 -
[1] Professional Committee of Liver Diseases, Chinese Association of Integrative Medicine. Diagnosis and treatment guidelines of integrated Chinese and western medicine for treating hepatic fibrosis (2019 ed)[J]. Chin J Integr Tradit West Med, 2019, 39(11): 1286-1295. DOI: 10.7661/j.cjim.20190916.314.中国中西医结合学会肝病专业委员会. 肝纤维化中西医结合诊疗指南(2019年版)[J]. 中国中西医结合杂志, 2019, 39(11): 1286-1295. DOI: 10.7661/j.cjim.20190916.314. [2] ROEB E. Matrix metalloproteinases and liver fibrosis (translational aspects)[J]. Matrix Biol, 2018, 68-69: 463-473. DOI: 10.1016/j.matbio.2017.12.012. [3] GBD 2015 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015[J]. Lancet, 2016, 388(10053): 1659-1724. DOI: 10.1016/S0140-6736(16)31679-8. [4] KISSELEVA T, BRENNER D. Molecular and cellular mechanisms of liver fibrosis and its regression[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(3): 151-166. DOI: 10.1038/s41575-020-00372-7. [5] SCHUPPAN D, ASHFAQ-KHAN M, YANG AT, et al. Liver fibrosis: Direct antifibrotic agents and targeted therapies[J]. Matrix Biol, 2018, 68-69: 435-451. DOI: 10.1016/j.matbio.2018.04.006. [6] ZHANG LJ, SCHUPPAN D. Traditional Chinese Medicine (TCM) for fibrotic liver disease: Hope and hype[J]. J Hepatol, 2014, 61(1): 166-168. DOI: 10.1016/j.jhep.2014.03.009. [7] NAN Y, DONG H, WANG ZG, et al. Research progress of animal experimental model of hepatic fibrosis[J]. China Med Herald, 2022, 19(12): 34-37. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202212008.htm南洋, 董辉, 王志刚, 等. 肝纤维化动物实验模型的研究进展[J]. 中国医药导报, 2022, 19(12): 34-37. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202212008.htm [8] RAVICHANDRA A, SCHWABE RF. Mouse models of liver fibrosis[M]//Methods in Molecular Biology. New York: Springer US, 2021: 339-356. DOI: 10.1007/978-1-0716-1382-5_23. [9] SHANG XF, YUAN HX, DAI LX, et al. Anti-liver fibrosis activity and the potential mode of action of Ruangan Granules: Integrated network pharmacology and metabolomics[J]. Front Pharmacol, 2022, 12: 754807. DOI: 10.3389/fphar.2021.754807. [10] YI JZ, WU SY, TAN SW, et al. Berberine alleviates liver fibrosis through inducing ferrous redox to activate ROS-mediated hepatic stellate cells ferroptosis[J]. Cell Death Discov, 2021, 7(1): 374. DOI: 10.1038/s41420-021-00768-7. [11] DING YF, WU ZH, WEI YJ, et al. Hepatic inflammation-fibrosis-cancer axis in the rat hepatocellular carcinoma induced by diethylnitrosamine[J]. J Cancer Res Clin Oncol, 2017, 143(5): 821-834. DOI: 10.1007/s00432-017-2364-z. [12] LOOMBA R, SANYAL AJ. The global NAFLD epidemic[J]. Nat Rev Gastroenterol Hepatol, 2013, 10(11): 686-690. DOI: 10.1038/nrgastro.2013.171. [13] LIU WW, SHANG JY, DENG YX, et al. Network pharmacology analysis on mechanism of Jian Pi Qing Gan Yin Decoction ameliorating high fat diet-induced non-alcoholic fatty liver disease and validated in vivo[J]. J Ethnopharmacol, 2022, 295: 115382. DOI: 10.1016/j.jep.2022.115382. [14] LIU LM, ZHOU Y, DAI D, et al. Protective effects of Kangxian Ruangan capsule against nonalcoholic fatty liver disease fibrosis in rats induced by MCD diet[J]. Biomed Pharmacother, 2018, 108: 424-434. DOI: 10.1016/j.biopha.2018.06.134. [15] ZHANG WF, WANG ZC. Research overview of molecular mechanism of TCM treatment of liver fibrosis[J]. Chin Arch Tradit Chin Med, 2022, 40(12): 119-124. DOI: 10.13193/j.issn.1673-7717.2022.12.024.张文富, 王振常. 中医药治疗肝纤维化分子机制的研究概况[J]. 中华中医药学刊, 2022, 40(12): 119-124. DOI: 10.13193/j.issn.1673-7717.2022.12.024. [16] ROEHLEN N, CROUCHET E, BAUMERT TF. Liver fibrosis: Mechanistic concepts and therapeutic perspectives[J]. Cells, 2020, 9(4): 875. DOI: 10.3390/cells9040875. [17] QIN LJ, LU Z, ZHENG ZH, et al. Research progress of natural products interfering with cell signaling pathway in liver fibrosis[J]. J Asian Nat Prod Res, 2022, 24(1): 15-23. DOI: 10.1080/10286020.2021.1883003. [18] DROPMANN A, DEDIULIA T, BREITKOPF-HEINLEIN K, et al. TGFβ1 and TGFβ2 abundance in liver diseases of mice and men[J]. Oncotarget, 2016, 7(15): 19499-19518. DOI: 10.18632/oncotarget.6967. [19] HAN DN, SU XL. Advances on TGFβ/Smad signal pathway in hepatic fibrosis[J]. Biomed Transform, 2021, 2(3): 49-56. DOI: 10.12287/j.issn.2096-8965.20210308.韩道宁, 苏秀兰. TGFβ/Smad信号通路在肝纤维化中的研究进展[J]. 生物医学转化, 2021, 2(3): 49-56. DOI: 10.12287/j.issn.2096-8965.20210308. [20] CHEN YJ, LI RF, HU N, et al. Baihe Wuyao Decoction ameliorates CCl4-induced chronic liver injury and liver fibrosis in mice through blocking TGFβ1/Smad2/3 signaling, anti-inflammation and anti-oxidation effects[J]. J Ethnopharmacol, 2020, 263: 113227. DOI: 10.1016/j.jep.2020.113227. [21] CAI FF, WU R, SONG YN, et al. Yinchenhao Decoction alleviates liver fibrosis by regulating bile acid metabolism and TGFβ/smad/ERK signalling pathway[J]. Sci Rep, 2018, 8(1): 15367. DOI: 10.1038/s41598-018-33669-4. [22] WANG L, LU W, GAO YH, et al. Effect of Anluohuaxianwan on the expression of matrix metalloproteinases and their inhibitors in rat liver with fibrosis[J]. Chin J Hepatol, 2019, 27(4): 267-273. DOI: 10.3760/cma.j.issn.l007-3418.2019.04.006.王林, 卢玮, 高玉华, 等. 安络化纤丸对肝纤维化大鼠肝组织基质金属蛋白酶及其抑制物表达的影响[J]. 中华肝脏病杂志, 2019, 27(4): 267-273. DOI: 10.3760/cma.j.issn.l007-3418.2019.04.006. [23] XIANG DJ, ZOU J, ZHU XY, et al. Physalin D attenuates hepatic stellate cell activation and liver fibrosis by blocking TGFβ/Smad and YAP signaling[J]. Phytomedicine, 2020, 78: 153294. DOI: 10.1016/j.phymed.2020.153294. [24] KANG R, TIAN W, CAO W, et al. Ligustroflavone ameliorates CCl4-induced liver fibrosis through down-regulating the TGFβ/Smad signaling pathway[J]. Chin J Nat Med, 2021, 19(3): 170-180. DOI: 10.1016/S1875-5364(21)60018-3. [25] HU NH, GUO CC, DAI XY, et al. Forsythiae Fructuse water extract attenuates liver fibrosis via TLR4/MyD88/NF-κB and TGFβ/smads signaling pathways[J]. J Ethnopharmacol, 2020, 262: 113275. DOI: 10.1016/j.jep.2020.113275. [26] LI S, GAN L, TIAN YJ, et al. Presegetane diterpenoids from Euphorbia sieboldiana as a new type of anti-liver fibrosis agents that inhibit TGFβ/Smad signaling pathway[J]. Bioorg Chem, 2021, 114: 105222. DOI: 10.1016/j.bioorg.2021.105222. [27] JIANG N, ZHANG J, PING J, et al. Salvianolic acid B inhibits autophagy and activation of hepatic stellate cells induced by TGFβ1 by downregulating the MAPK pathway[J]. Front Pharmacol, 2022, 13: 938856. DOI: 10.3389/fphar.2022.938856. [28] ZHAO YC, LIU XL, DING CB, et al. Aronia melanocarpa polysaccharide ameliorates liver fibrosis through TGFβ1-mediated the activation of PI3K/AKT pathway and modulating gut microbiota[J]. J Pharmacol Sci, 2022, 150(4): 289-300. DOI: 10.1016/j.jphs.2022.10.001. [29] TIAN T. Study of fuzhenghayukangxian decoction on the expression of TGFβ1 and PDGF of hepatic fibrosis rats[D]. Lanzhou: Gansu University of Chinese Medicine, 2016.田甜. 扶正化瘀抗纤方对肝纤维化大鼠TGFβ1及PDGF表达的影响研究[D]. 兰州: 甘肃中医药大学, 2016. [30] WANG L, YAN HJ, CAO X, et al. Effects of Qianggan capsule on TGFβ1 and PDGF-BB in rats with liver fibrosis induced by carbon tetrachloride[J]. Chin J Integr Tradit West Med Liver Dis, 2020, 30(4): 341-345, 386. DOI: 10.3969/j.issn.1005-0264.2020.04.016.王林, 闫海江, 曹曦, 等. 强肝胶囊对CCl4诱导的肝纤维化大鼠肝组织TGFβ1和PDGF-BB的影响[J]. 中西医结合肝病杂志, 2020, 30(4): 341-345, 386. DOI: 10.3969/j.issn.1005-0264.2020.04.016. [31] LI JB. Effects of Corydalis extract on hepatic fibrosis in rats and its effects on PDGF signaling pathway[D]. Hangzhou: Zhejiang Chinese Medical University, 2017.李剑波. 延胡索提取物对肝纤维化大鼠的治疗作用及其对PDGF信号通路转导的影响[D]. 杭州: 浙江中医药大学, 2017. [32] ZHANG XS, LYU YH, WANG YH, et al. Influence of Danhong Rangan capsule on serum PDGF level in patients with chronic hepatitis B[J]. Chin J Integr Tradit West Med Liver Dis, 2012, 22(4): 208-209. DOI: 10.3969/j.issn.1005-0264.2012.04.005.张希顺, 吕宇航, 王玉红, 等. 丹红软肝胶囊对肝纤维化患者血小板生长因子的影响[J]. 中西医结合肝病杂志, 2012, 22(4): 208-209. DOI: 10.3969/j.issn.1005-0264.2012.04.005. [33] CHEN Q, CHEN LY, KONG DS, et al. Dihydroartemisinin alleviates bile duct ligation-induced liver fibrosis and hepatic stellate cell activation by interfering with the PDGF-βR/ERK signaling pathway[J]. Int Immunopharmacol, 2016, 34: 250-258. DOI: 10.1016/j.intimp.2016.03.011. [34] WANG KS. Effect of Shugan heluo xingpi decoction on Wnt/β-catenin signaling pathway in CCl4 hepatic fibrosis rats[D]. Lanzhou: Gansu University of Chinese Medicine, 2022.王奎淞. 基于Wnt/β-Catenin信号通路探讨舒肝和络醒脾方抗肝纤维化作用机制研究[D]. 兰州: 甘肃中医药大学, 2022. [35] SUN X, XIONG F, HUANG YS, et al. Effect of Gexia Zhuyu Decoction on Wnt/β-catenin pathway in rats with hepatic fibrosis induced by carbon tetrachloride[J]. Chin Tradit Pat Med, 2022, 44(6): 1945-1950. DOI: 10.3969/j.issn.1001-1528.2022.06.039.孙旭, 熊芬, 黄育生, 等. 膈下逐瘀汤对四氯化碳诱导的肝纤维化大鼠Wnt/β-catenin通路的影响[J]. 中成药, 2022, 44(6): 1945-1950. DOI: 10.3969/j.issn.1001-1528.2022.06.039. [36] ZHOU YC. Clinical and experimental study of chaiqiyiganfang in treating hepatic fibrosis[D]. Beijing: Beijing University of Chinese Medicine, 2021.周怡驰. 柴芪益肝方治疗肝纤维化的临床和实验研究[D]. 北京: 北京中医药大学, 2021. [37] LIU JP, GUO XZ, LI XM, et al. Effect of Silibinin capsules on liver fibrosis and Wnt/β-catenin signaling pathways in patients with chronic HBV infection[J]. Chin J Nosocomiology, 2022, 32(3): 336-340. DOI: 10.11816/cn.ni.2022-210538.刘俊平, 郭新忠, 李晓敏, 等. 水飞蓟宾胶囊对慢性HBV感染患者肝纤维化Wnt/β-catenin信号通路的影响[J]. 中华医院感染学杂志, 2022, 32(3): 336-340. DOI: 10.11816/cn.ni.2022-210538. [38] LI HY. The effects of Cynomorium songaricum on hepatic fibrosis mice and its hedgehog signaling pathway[D]. Chengdu: Chengdu Medical College, 2017.李卉园. 锁阳对小鼠肝纤维化及其对Hedgehog信号通路干预作用的初步探讨[D]. 成都: 成都医学院, 2017. [39] LIN X, LI J, XING YQ. Geniposide, a sonic hedgehog signaling inhibitor, inhibits the activation of hepatic stellate cell[J]. Int Immunopharmacol, 2019, 72: 330-338. DOI: 10.1016/j.intimp.2019.04.016. [40] GAO H, WEN N, XU XS, et al. Endoplasmic reticulum stress enhances tumor necrosis factor-α expression in rat Kupffer cells to trigger hepatic stellate apoptosis cell through TNFR/caspase-8 pathway[J]. J South Med Univ, 2020, 40(5): 632-639. DOI: 10.12122/j.issn.1673-4254.2020.05.04.高宏, 文楠, 徐雪松, 等. 内质网应激介导的Kupffer细胞源性TNF-α经TNFR/caspase 8途径诱导肝星状细胞凋亡[J]. 南方医科大学学报, 2020, 40(5): 632-639. DOI: 10.12122/j.issn.1673-4254.2020.05.04. [41] LI MS, ZHANG GX, WEI YY, et al. Study on the regulatory mechanism of Yinchenhao decoction on proliferation and apoptosis of alcoholic liver fibrosis[J]. J Sichuan Tradit Chin Med, 2020, 38(2): 52-54. https://www.cnki.com.cn/Article/CJFDTOTAL-SCZY202002019.htm李木松, 张贵贤, 魏媛媛, 等. 茵陈蒿汤对酒精性肝纤维化的增殖及凋亡的调节机制研究[J]. 四川中医, 2020, 38(2): 52-54. https://www.cnki.com.cn/Article/CJFDTOTAL-SCZY202002019.htm [42] MENG P, NAN YM, ZHAO SX. Effect of Yiqi Huoxue recipe on hepatocyte apoptosis in rats with hepatic fibrosis[J]. J Hebei Tradit Chin Med Pharmacol, 2020, 35(6): 1-5. DOI: 10.16370/j.cnki.13-1214/r.2020.06.001.孟萍, 南月敏, 赵素贤. 益气活血方对肝纤维化大鼠肝细胞凋亡的影响[J]. 河北中医药学报, 2020, 35(6): 1-5. DOI: 10.16370/j.cnki.13-1214/r.2020.06.001. [43] YU YN, ZHONG J, LIU XY, et al. Effect of Dahuang Zhechong Pills on hepatic histopathology and apoptosis in rats with experimental hepatic fibrosis[J]. Drugs & Clin, 2020, 35(2): 197-201. DOI: 10.7501/j.issn.1674-5515.2020.02.001.于亚男, 钟俊, 刘晓雨, 等. 大黄蛰虫丸对实验性肝纤维化大鼠肝组织病理学及其细胞凋亡的影响[J]. 现代药物与临床, 2020, 35(2): 197-201. DOI: 10.7501/j.issn.1674-5515.2020.02.001. [44] ZHANG XL, CHEN ZN, HUANG QF, et al. Methyl helicterate inhibits hepatic stellate cell activation through modulation of apoptosis and autophagy[J]. Cell Physiol Biochem, 2018, 51(2): 897-908. DOI: 10.1159/000495390. [45] LI YJ. Autophagy mediated by endoplasmic reticulum stress enhances caffeine-induced apoptosis of hepatic stellate cells[D]. Shanghai: Shanghai Jiao Tong University, 2017.李勇剑. 咖啡因通过增强内质网应激介导的细胞自噬而诱导肝星形细胞凋亡[D]. 上海: 上海交通大学, 2017. [46] ZHANG XL, HAN X, YIN LH, et al. Potent effects of dioscin against liver fibrosis[J]. Sci Rep, 2015, 5: 9713. DOI: 10.1038/srep09713. [47] CHE XH, PARK EJ, ZHAO YZ, et al. Tanshinone Ⅱ A induces apoptosis and S phase cell cycle arrest in activated rat hepatic stellate cells[J]. Basic Clin Pharmacol Toxicol, 2010, 106(1): 30-37. DOI: 10.1111/j.1742-7843.2009.00465.x. [48] WAN YP, ZHANG W, ZHU X. Research advance in the role of pyroptosis in the development and progression of liver fibrosis[J]. China J Mod Med, 2021, 31(24): 69-74. DOI: 10.3969/j.issn.1005-8982.2021.24.012.万义鹏, 张望, 朱萱. 细胞焦亡在肝纤维化发生、发展中的作用研究进展[J]. 中国现代医学杂志, 2021, 31(24): 69-74. DOI: 10.3969/j.issn.1005-8982.2021.24.012. [49] XIE ZY, XU YX, ZHENG MY, et al. Based on network pharmacology, the anti-scorching effect of acacia bark and tribulus terrestris on inhibiting hepatic stellate cell line LX2[J]. China J Chin Mater Med, 2023, 48(2): 481-491. DOI: 10.19540/j.cnki.cjcmm.20221011.401.谢泽宇, 许一笑, 郑梦圆, 等. 基于网络药理学探究合欢皮-白蒺藜药对抑制肝星状细胞系LX2的抗焦亡作用[J]. 中国中药杂志, 2023, 48(2): 481-491. DOI: 10.19540/j.cnki.cjcmm.20221011.401. [50] ZHOU ZP, QIN L, NONG RN, et al. Effects of Isodon ternifolia on NLRP3/caspase-1/GSDMD signaling pathway in rats with hepatic fibrosis induced by CCl4[J]. Pharmacol Clin Chin Mater Med, 2021, 37(4): 96-101. DOI: 10.13412/j.cnki.zyyl.20210707.002.周至品, 覃乐, 农汝楠, 等. 三叶香茶菜对CCl4致肝纤维化大鼠NLRP3/Caspase-1/GSDMD信号通路的影响[J]. 中药药理与临床, 2021, 37(4): 96-101. DOI: 10.13412/j.cnki.zyyl.20210707.002. [51] HUANG Y, XIA L, LEI QS, et al. Protective effects and mechanism of saikosaponin D on immune hepatic fibrosis in rats[J]. J Army Med Univ, 2022, 44(14): 1410-1420. DOI: 10.16016/j.2097-0927.202111062.黄祎, 夏莉, 雷青松, 等. 柴胡皂苷D对大鼠免疫性肝纤维化的保护作用及其机制研究[J]. 陆军军医大学学报, 2022, 44(14): 1410-1420. DOI: 10.16016/j.2097-0927.202111062. [52] GAO JH, WEI B, de ASSUNCAO TM, et al. Hepatic stellate cell autophagy inhibits extracellular vesicle release to attenuate liver fibrosis[J]. J Hepatol, 2020, 73(5): 1144-1154. DOI: 10.1016/j.jhep.2020.04.044. [53] DING JB, LI XH. Current perspectives on the role of autophagy in liver fibrosis[J]. J Clin Hepatol, 2013, 29(4): 305-307. DOI: 10.3969/j.issn.1001-5256.2013.04.018.丁剑波, 李秀惠. 细胞自噬在肝纤维化中的作用[J]. 临床肝胆病杂志, 2013, 29(4): 305-307. DOI: 10.3969/j.issn.1001-5256.2013.04.018. [54] HUANG LW, JIANG N, PING J, et al. Study on anti-fibrotic mechanism of Fuzheng-Huayu formula to suppress autophagy in mice[J]. Chin J Hepatol, 2019, 27(8): 621-627. DOI: 10.3760/cma.j.issn.1007-3418.2019.08.007.黄兰蔚, 姜娜, 平键, 等. 扶正化瘀复方抑制小鼠自噬的抗纤维化机制研究[J]. 中华肝脏病杂志, 2019, 27(8): 621-627. DOI: 10.3760/cma.j.issn.1007-3418.2019.08.007. [55] WANG BY. Yiqi Huoxue recipe ameliorates carbon tetrachloride-induced liver fibrosis by inhibiting autophagy in rats[D]. Shijiazhuang: Hebei Medical University, 2017.王宝玉. 益气活血方调节肝脏细胞自噬及逆转肝纤维化机制的研究[D]. 石家庄: 河北医科大学, 2017. [56] ZHANG YQ, HUA LP, LIN CF, et al. Pien-Tze-Huang alleviates CCl4-induced liver fibrosis through the inhibition of HSC autophagy and the TGFβ1/Smad2 pathway[J]. Front Pharmacol, 2022, 13: 937484. DOI: 10.3389/fphar.2022.937484. [57] CHEN SY, HE ZW, XIE W, et al. Ginsenoside Rh2 attenuates CDAHFD-induced liver fibrosis in mice by improving intestinal microbial composition and regulating LPS-mediated autophagy[J]. Phytomedicine, 2022, 101: 154121. DOI: 10.1016/j.phymed.2022.154121. [58] LI C. Study on the mechanism of berberine on regulation of hepatic stellate cell autophagy and liver fibrosis[D]. Chengdu: Chengdu Medical College, 2020.李灿. 小檗碱调控肝星状细胞自噬及其对肝纤维化作用的机制研究[D]. 成都: 成都医学院, 2020. [59] HERNÁNDEZ-AQUINO E, QUEZADA-RAMÍREZ MA, SILVA-OLIVARES A, et al. Curcumin downregulates Smad pathways and reduces hepatic stellate cells activation in experimental fibrosis[J]. Ann Hepatol, 2020, 19(5): 497-506. DOI: 10.1016/j.aohep.2020.05.006. [60] CHEN WW, ZHANG ZL, YAO Z, et al. Activation of autophagy is required for Oroxylin A to alleviate carbon tetrachloride-induced liver fibrosis and hepatic stellate cell activation[J]. Int Immunopharmacol, 2018, 56: 148-155. DOI: 10.1016/j.intimp.2018.01.029. [61] WANG R, SONG MY, LI XW, et al. Alterations in intestinal flora and hepatic fibrosis[J]. World Chin J Dig, 2014, 22(26): 3937-3940. https://www.cnki.com.cn/Article/CJFDTOTAL-XXHB201426012.htm王蓉, 宋明宇, 李学文, 等. 肠道菌群改变与肝纤维化相互作用的研究进展[J]. 世界华人消化杂志, 2014, 22(26): 3937-3940. https://www.cnki.com.cn/Article/CJFDTOTAL-XXHB201426012.htm [62] LI NN, MENG XS, GUO WZ, et al. Effect of Ruangan Granule on CCl4-induced liver fibrosis and intestinal flora in rats[J/OL]. Liaoning J Tradit Chin Med, 2022. [Online ahead of print]李楠楠, 孟宪生, 郭文昭, 等. 软肝冲剂对CCl4诱导大鼠肝纤维化及肠道菌群的影响研究[J/OL]. 辽宁中医杂志, 2022. [网络首发] [63] WEI X. Based on the entero-hepatic axis, the mechanism of Ganshuang Granules regulating intestinal flora in the treatment of liver fibrosis was studied[D]. Tianjin: Tianjin University of Traditional Chinese Medicine, 2021.魏鑫. 基于肠-肝轴研究肝爽颗粒调节肠道菌群治疗肝纤维化的作用机制[D]. 天津: 天津中医药大学, 2021. [64] NIE Y. Exploring the mechanism of ursolic acid inhibit liver fibrosis based on intestinal bacteria-liver bile acids axis[D]. Nanchang: Nanchang University, 2022.聂源. 基于肠道菌-肝胆汁酸轴探究熊果酸抑制肝纤维化的作用机制[D]. 南昌: 南昌大学, 2022. [65] XU J, QI L, ZHOU T, et al. Clinical study on prevention and treatment of chronic hepatitis B liver fibrosis with Kangxianruangan Granule on gut microbiota[J]. Chin J Integr Tradit West Med Liver Dis, 2021, 31(9): 776-780. DOI: 10.3969/j.issn.1005-0264.2021.09.002.徐俊, 戚璐, 周涛, 等. 从肠道菌群探讨抗纤软肝颗粒防治慢性乙型肝炎肝纤维化的临床研究[J]. 中西医结合肝病杂志, 2021, 31(9): 776-780. DOI: 10.3969/j.issn.1005-0264.2021.09.002. [66] SUN LX. Advancement in experimental investigation on treatment of fibrosis with traditional Chinese medicine[J]. Jiangsu J Tradit Chin Med, 2001, 8: 46-48. https://www.cnki.com.cn/Article/CJFDTOTAL-JSZY200108034.htm孙丽霞. 中药抗肝纤维化的实验研究进展[J]. 江苏中医, 2001, 8: 46-48. https://www.cnki.com.cn/Article/CJFDTOTAL-JSZY200108034.htm [67] LI H. Advances in anti hepatic fibrotic therapy with Traditional Chinese Medicine herbal formula[J]. J Ethnopharmacol, 2020, 251: 112442. DOI: 10.1016/j.jep.2019.112442. [68] WEI CL, QIU J, WU YY, et al. Promising traditional Chinese medicine for the treatment of cholestatic liver disease process (cholestasis, hepatitis, liver fibrosis, liver cirrhosis)[J]. J Ethnopharmacol, 2022, 297: 115550. DOI: 10.1016/j.jep.2022.115550.
计量
- 文章访问数: 1288
- HTML全文浏览量: 492
- PDF下载量: 279
- 被引次数: 0