扶正化瘀方治疗慢性肝病的临床与基础研究进展

关茜; 刘伟; 陈佳美; 慕永平; 刘平; 徐莹

doi:10.3969/j.issn.1001-5256.2021.06.048

扶正化瘀方治疗慢性肝病的临床与基础研究进展

DOI: 10.3969/j.issn.1001-5256.2021.06.048

关茜^1a,
刘伟^{1b, 2, 3},
陈佳美^{1b, 2, 3},
慕永平^{1b, 2, 3},
刘平^1b,
徐莹^1a,

1a.
上海中医药大学教学实验中心，上海 20120
1b.
上海中医药大学肝病研究所，上海 201203
2.
上海中医药大学附属曙光医院肝硬化科，上海 201203
3.
肝肾疾病病证教育部重点实验室，上海 201203

基金项目:

上海市青年科技英才扬帆计划 (20yf1449500);

国家自然基金青年科学基金 (82004162);

中国博士后基金 (2020M681367)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：关茜负责查阅文章，撰写论文；刘伟、陈佳美、慕永平参与查阅文献，修改论文；徐莹、刘平负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

作者简介:
关茜(1992—)，女，主要从事中医四诊客观化、规范化方面的研究

徐莹，xuying.911@163.com

中图分类号: R575
计量
- 文章访问数: 1100
- HTML全文浏览量: 481
- PDF下载量: 109
- 被引次数: 0
出版历程
- 收稿日期: 2020-11-15
- 录用日期: 2020-12-30
- 出版日期: 2021-06-20

Research advances in the clinical and basic research on Fuzheng Huayu prescription in treatment of chronic liver diseases

Xi GUAN^1a,
Wei LIU^{1b, 2, 3},
Jiamei CHEN^{1b, 2, 3},
Yongping MU^{1b, 2, 3},
Ping LIU^1b,
Ying XU^{1a
,}

1a.
Teaching and Experiment Center, , Shanghai 201203, China
1b.
Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 201203
2.
Department of Liver Cirrhosis, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
3.
Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai 201203, China

摘要

摘要: 扶正化瘀方由上海中医药大学研制，具有活血化瘀，养精益肝功效，是治疗慢性病毒性肝炎、非酒精性脂肪性肝病、肝纤维化、肝硬化及肝癌等慢性肝病的有效验方。该方已临床应用多年，在缓解临床症状、改善肝纤维化程度及并发症等方面疗效显著。近年来，不少学者对扶正化瘀方治疗慢性肝病的临床效果和作用机制开展了深入研究，并取得满意成果，现作一总结，为后续研究提供参考。
- 肝疾病 /
- 扶正化瘀方 /
- 治疗学
Abstract: Fuzheng Huayu prescription is developed by Shanghai University of Traditional Chinese Medicine and has the functions of promoting blood circulation, removing blood stasis, nourishing essence, and tonifying the liver, and it is an effective empirical prescription for the treatment of chronic liver diseases including chronic viral hepatitis, nonalcoholic fatty liver disease, liver fibrosis, liver cirrhosis, and liver cancer. This prescription has been used in clinical practice for many years and has a marked clinical effect in alleviating clinical symptoms and improving liver fibrosis and complications. In recent years, many scholars have conducted in-depth studies on the clinical effect and mechanism of action of Fuzheng Huayu prescription in the treatment of chronic liver diseases and achieved satisfactory results. This article summarizes related research findings in order to provide a reference for subsequent studies.
- Liver Disease /
- Fuzhenghuayu Formula /
- Therapeutics

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参考文献(40)

[1]	ZHONG KY, LIU TJ. Clinical features of chronic liver disease and notion of syndrome differentiation in Traditional Chinese Medicine[J/CD]. Cardiov Dis J Integr Tradit Chin Western Med(Electronic), 2019, 7(21): 155. 钟岢屹, 刘铁军. 慢性肝病的临床特点及中医辩证治疗体会[J/CD]. 中西医结合心血管病电子杂志, 2019, 7(21): 155.
[2]	YANG T, LIU S, WANG CH, et al. Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe[J]. J Pharm Biomed Anal, 2015, 114: 152-158. DOI: 10.1016/j.jpba.2015.05.014.
[3]	LIU YY, LIU YP, LIU YR, et al. Implementation of aerobic exercise intervention in patients with metabolic associated fatty liver disease: A prospective study[J]. J Clin Hepatol, 2020, 36(11): 2467-2472. DOI: 10.3969/j.issn.1001-5256.2020.11.014. 刘莹莹, 刘玉萍, 刘佑韧, 等. 代谢相关脂肪性肝病患者有氧运动干预实施的前瞻性研究[J]. 临床肝胆病杂志, 2020, 36(11): 2467-2472. DOI: 10.3969/j.issn.1001-5256.2020.11.014.
[4]	XU YH, FAN JG. Progress in pharmacotherapy of nonalcoholic fatty liver disease[J]. Shanghai Med Pharm J, 2020, 41(19): 3-6, 11. https://www.cnki.com.cn/Article/CJFDTOTAL-SYIY202019002.htm 许炎煌, 范建高. 非酒精性脂肪性肝病治疗药物研究进展[J]. 上海医药, 2020, 41(19): 3-6, 11. https://www.cnki.com.cn/Article/CJFDTOTAL-SYIY202019002.htm
[5]	YU JP, FENG LY, CHEN X, et al. Polyene phosphatidyl choline joint fuzheng huayu capsule in treating nonalcoholic fatty hepatitis[J]. Chin J Gen Prac, 2014, 12(8): 1325-1326. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY201408052.htm 俞建平, 冯兰英, 陈霞, 等. 多烯磷脂酰胆碱联合扶正化瘀胶囊治疗非酒精性脂肪性肝炎的临床疗效[J]. 中华全科医学, 2014, 12(8): 1325-1326. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY201408052.htm
[6]	ZHENG W, SU LW, ZHAO BL. Treatment of 34 cases of moderate and severe non-alcoholic steatohepatitis with Fuzheng Huayu capsule and silybin capsule[J]. Chin J Integr Tradit West Med Liver Dis, 2015, 25(3): 177-178. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXGB201503021.htm 郑伟, 苏立稳, 赵宝丽. 扶正化瘀胶囊联合水飞蓟宾胶囊治疗中重度非酒精性脂肪性肝炎34例[J]. 中西医结合肝病杂志, 2015, 25(3): 177-178. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXGB201503021.htm
[7]	LI Y, LIU WT, KE WB. Clinical analysis of Fuzheng Huayu capsule combined with insulin sensitizer in the treatment of non-alcoholic steatohepatitis[J]. Mod J Integr Tradit Chin West Med, 2017, 26(24): 2665-2667. DOI: 10.3969/j.issn.1008-8849.2017.24.015. 李亚, 刘文涛, 柯文炳. 扶正化瘀胶囊联合胰岛素增敏剂治疗非酒精性脂肪性肝炎临床分析[J]. 现代中西医结合杂志, 2017, 26(24): 2665-2667. DOI: 10.3969/j.issn.1008-8849.2017.24.015.
[8]	ZHU D. Research on the regularity of syndrome and treatment of fatty liver disease by famous veteran TCM docotors and exploration of knowledge map construction[D]. Beijing: China Academy of Chinese Medical Sciences, 2019. 朱丹. 名老中医治疗脂肪性肝病的证治规律研究及知识图谱构建探索[D]. 北京: 中国中医科学院, 2019.
[9]	HUO MM, CHENG BQ, LIN WG, et al. Therapeutic effects of Fuzheng huayu decoction on non-alcoholic steatohepatic fibrosis rats by regulating ACE-Ang Ⅱ-AT1R axis[J]. Med J Chin PLA, 2018, 43(2): 114-119. DOI: 10.11855/j.issn.0577-7402.2018.02.05. 霍苗苗, 程变巧, 林伟国, 等. 扶正化瘀方对非酒精性脂肪性肝病大鼠肝纤维化及ACE-Ang Ⅱ-AT1R轴的影响[J]. 解放军医学杂志, 2018, 43(2): 114-119. DOI: 10.11855/j.issn.0577-7402.2018.02.05.
[10]	WANG RQ, MI HM, LI H, et al. Modulation of IKKβ/NF-κB and TGF-β1/Smad via Fuzheng Huayu recipe involves in prevention of nutritional steatohepatitis and fibrosis in mice[J]. Iran J Basic Med Sci, 2015, 18(4): 404-411. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439457/
[11]	KONG YY, SUN YM, ZHOU JL, et al. Association between the reduction in liver stiffness measurement and the histological outcome of liver fibrosis regression in patients with chronic hepatitis B[J]. J Clin Hepatol, 2020, 36(2): 314-318. DOI: 10.3969/j.issn.1001-5256.2020.02.016. 孔媛媛, 孙亚朦, 周家玲, 等. 慢性乙型肝炎患者肝脏硬度值下降趋势与肝纤维化逆转结局的关系[J]. 临床肝胆病杂志, 2020, 36(2): 314-318. DOI: 10.3969/j.issn.1001-5256.2020.02.016.
[12]	GUI HL, ZHAO CQ, WANG Y, et al. Histological outcome of Fuzheng Huayu plus entecavir combination therapy in chronic hepatitis B patients with significant liver fibrosis[J]. J Clin Transl Hepatol, 2020, 8(3): 277-284. DOI: 10.14218/JCTH.2020.00004.
[13]	XIE HS, CAI LM, YAN MH. Entecavir combined with Fuzheng Huayu capsule for treatment hepatic fibrosis in chronic hepatitis B patients[J]. Zhejiang Med J, 2016, 38(8): 555-557. https://www.cnki.com.cn/Article/CJFDTOTAL-ZJYE201608012.htm 谢宏晟, 蔡丽敏, 颜鸣鹤. 恩替卡韦联合扶正化瘀胶囊治疗慢性乙型肝炎肝纤维化的效果观察[J]. 浙江医学, 2016, 38(8): 555-557. https://www.cnki.com.cn/Article/CJFDTOTAL-ZJYE201608012.htm
[14]	XIA XF, WU J, GONG L, et al. Effect of Fuzheng Huayu capsule on liver hardness level of chronic hepatitis B with hepatic fibrosis[J]. Chin J Integr Tradit West Med Liver Dis, 2019, 29(6): 500-501. DOI: 10.3969/j.issn.1005-0264.2019.06.007. 夏小芳, 吴建, 龚玲, 等. 扶正化瘀胶囊联合恩替卡韦对慢性乙型肝炎患者肝纤维化程度的影响[J]. 中西医结合肝病杂志, 2019, 29(6): 500-501. DOI: 10.3969/j.issn.1005-0264.2019.06.007.
[15]	WANG H, WANG QJ, SUN FB, et al. Effect of entecavir combined with Fuzheng Huayu capsules on inflammatory factors and fibrosis markers in patients with compensated chronic hepatitis B-related cirrhosis[J]. J Clin Hepatol, 2016, 32 (9): 1734-1738. DOI: 10.3969/j.issn.1001-5256.2016.09.020. 王贺, 王千钧, 孙风波, 等. 恩替卡韦联合扶正化瘀胶囊对代偿期慢性乙型肝炎肝硬化患者炎性因子及纤维化指标的影响[J]. 临床肝胆病杂志, 2016, 32(9): 1734-1738. DOI: 10.3969/j.issn.1001-5256.2016.09.020.
[16]	ZHANG LM, ZHANG QL. Clinical effect and the safety of entecavir combined with Fuzheng Huayu capsule in the treatment of decompensated hepatitis B cirrhosis[J]. Chin J Clin Ration Drug Use, 2017, 10(33): 7-8. DOI: 10.15887/j.cnki.13-1389/r.2017.33.004. 张雷鸣, 张庆丽. 恩替卡韦联合扶正化瘀胶囊治疗失代偿期乙型肝炎肝硬化的临床疗效及安全性[J]. 临床合理用药杂志, 2017, 10(33): 7-8. DOI: 10.15887/j.cnki.13-1389/r.2017.33.004.
[17]	LI XY, ZHANG GS. Clinical effect of Fuzheng Huayu Capsules combined with Magnesium Isoglycerate in the treatment of decompensated cirrhosis[J]. China Med Herald, 2019, 16(11): 138-141. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY201911035.htm 李晓永, 张国顺. 扶正化瘀胶囊联合异甘草酸镁治疗失代偿期肝硬化患者的临床效果[J]. 中国医药导报, 2019, 16(11): 138-141. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY201911035.htm
[18]	LI H, XU XL, ZHENG TT, et al. Effects of sophora flavescens preparation combined with Fuzheng Huayu capsules on hepatic hemodynamics and fibrosis indexes in patients with hepatitis B liver cirrhosis[J]. China Pharm, 2017, 28(8): 1114-1116. DOI: 10.6039/j.issn.1001-0408.2017.08.30. 李洪, 许小莉, 郑婷婷, 等. 苦参制剂联合扶正化瘀胶囊对乙型肝炎肝硬化患者肝血流动力学及纤维化指标的影响[J]. 中国药房, 2017, 28(8): 1114-1116. DOI: 10.6039/j.issn.1001-0408.2017.08.30.
[19]	LI YX, ZHANG FY, CUI Z. Efficacy of ursodeoxycholic acid combined with Fuzheng Huayu Capsule in the treatment of HBeAg-positive patients with high viral load hepatitis B cirrhosis and its effect on liver fibrosis and inflammatory factors[J]. Mod J Integr Tradit Chin West Med, 2018, 27(18): 2016-2019. DOI: 10.3969/j.issn.1008-8849.2018.18.025. 李玉贤, 张汾燕, 崔振. 熊去氧胆酸联合扶正化瘀胶囊治疗HBeAg阳性高病毒载量乙肝肝硬化患者的疗效及对肝纤维化和炎性因子的影响[J]. 现代中西医结合杂志, 2018, 27(18): 2016-2019. DOI: 10.3969/j.issn.1008-8849.2018.18.025.
[20]	MA X, LIAO QY, HE X, et al. Systematic review on Fuzhenghuayu capsules combined with entecavir in the treatment of liver fibrosis induced by chronic hepatitis B[J]. Eval Anal Drug-Use in Hosp China, 2019, 19(12): 1413-1419. DOI: 10.14009/j.issn.1672-2124.2019.12.002. 马骁, 廖庆英, 何璇, 等. 扶正化瘀胶囊联合恩替卡韦治疗慢性乙型肝炎肝纤维化的系统评价[J]. 中国医院用药评价与分析, 2019, 19(12): 1413-1419. DOI: 10.14009/j.issn.1672-2124.2019.12.002.
[21]	WANG J, PENG FC. Meta-analysis on indirect comparison of Fuzheng Huayu Jiaonang and Anluo Huaxian Wan in treatment of chronic hepatitis B with liver fibrosis[J]. China J Chin Mater Med, 2018, 43(7): 1492-1500. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZY201807028.htm 王晶, 彭芳辰. 扶正化瘀胶囊与安络化纤丸治疗慢性乙型肝炎肝纤维化疗效的间接Meta分析[J]. 中国中药杂志, 2018, 43(7): 1492-1500. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZY201807028.htm
[22]	WANG H, HE HF, LIU LP, et al. Systematic evalution of Fuzheng Huayu Capsule combined with Adefovir Dipivoxil in treatment of chronic hepatitis B with hepatic fibrosis[J]. Chin Tradit Herb Drug, 2017, 48(18): 3876-3884. DOI: 10.7501/j.issn.0253-2670.2017.18.031. 王欢, 何惠芳, 刘丽萍, 等. 扶正化瘀胶囊联合阿德福韦酯治疗慢性乙型肝炎肝纤维化的系统评价[J]. 中草药, 2017, 48(18): 3876-3884. DOI: 10.7501/j.issn.0253-2670.2017.18.031.
[23]	LIU GT, LAN BZ, LIANG Z. et al. Meta-analysis of lamivudine combined Fuzheng Huayu capsule in treatment of chronic hepatitis B liver fibrosis[J]. Liaoning J Tradit Chin Med, 2016, 43(10): 2026-2031. DOI: 10.13192/j.issn.1000-1719.2016.10.003. 刘钢涛, 蓝柏钊, 梁真, 等. 拉米夫定联合扶正化瘀胶囊治疗慢性乙型肝炎肝纤维化疗效的Meta分析[J]. 辽宁中医杂志, 2016, 43(10): 2026-2031. DOI: 10.13192/j.issn.1000-1719.2016.10.003.
[24]	WANG B, LONG YX, LI HM, et al. Fuzheng Huayu capsule combined with Nucleoside antiviral drugs therapy in hepatitis B cirrhosis: A systematic review[J]. J Public Health Prev Med, 2015, 26(5): 9-13. https://www.cnki.com.cn/Article/CJFDTOTAL-FBYF201505003.htm 王彬, 龙远雄, 李瀚旻, 等. 扶正化瘀胶囊联合核苷(酸)类抗病毒药物治疗乙型肝炎肝硬化的系统评价[J]. 公共卫生与预防医学, 2015, 26(5): 9-13. https://www.cnki.com.cn/Article/CJFDTOTAL-FBYF201505003.htm
[25]	WANG T, ZHOU X, LIU H, et al. Fuzheng Huayu capsule as an adjuvant treatment for HBV-related cirrhosis: A systematic review and meta-analysis[J]. Phytother Res, 2018, 32(5): 757-768. DOI: 10.1002/ptr.6009.
[26]	CHEN Y, ZHAO Z, FAN H, et al. Safety and therapeutic effects of anti-fibrotic Traditional Chinese Medicine Fuzheng Huayu on persistent advanced stage fibrosis following 2 years entecavir treatment: Study protocol for a single arm clinical objective performance criteria trial[J]. Contemp Clin Trials Commun, 2020, 19: 100601. DOI: 10.1016/j.conctc.2020.100601.
[27]	LI ZX, ZHAO ZM, LIU P, et al. Treatment of HBV cirrhosis with Fuzheng Huayu tablet and entecavir: Design of a randomized, double-blind, parallel and multicenter clinical trial[J]. Chin J Integr Med, 2020. DOI: 10.1007/s11655-020-3257-6.[Online ahead of print]
[28]	ZHENG YL. Dynamic changes of IGF-1 in the development of hepatic fibrosis in rats and effects of Fuzheng huayu on hepatic fibrosis[D]. Shijiazhuang: Hebei Medical University, 2011. 郑艳丽. IGF-1在大鼠肝纤维化过程中的动态变化及扶正化瘀方对肝纤维化的影响[D]. 石家庄: 河北医科大学, 2011.
[29]	WU R, DONG S, CAI FF, et al. Active compounds derived from Fuzheng Huayu formula protect hepatic parenchymal cells from apoptosis based on network pharmacology and transcriptomic analysis[J]. Molecules, 2019, 24(2): 338. DOI: 10.3390/molecules24020338.
[30]	YI WH, LI Y, XIE SB. Therapeutic effects of Fuzheng Huayu decoction in different pathological stages CCl4-induced liver cirrhosis rat model and on hepatic stellate cells activation[J]. J Pract Med, 2014, 30(9): 1366-1369. DOI: 10.3969/j.issn.1006-5725.2014.09.008. 易文华, 李烨, 谢仕斌. 扶正化瘀方对不同病理阶段四氯化碳大鼠肝纤维化及活化星状细胞的影响[J]. 实用医学杂志, 2014, 30(9): 1366-1369. DOI: 10.3969/j.issn.1006-5725.2014.09.008.
[31]	TAO YY, YAN XC, ZHOU T, et al. Fuzheng Huayu recipe alleviates hepatic fibrosis via inhibiting TNF-α induced hepatocyte apoptosis[J]. BMC Complement Altern Med, 2014, 14: 449. DOI: 10.1186/1472-6882-14-449.
[32]	XING XR. Muti-target based mechanism investigation of Fuzheng Huayu formula in treatment liver fibrosis[D]. Chongqing: The Second Military Medical University, 2019. 邢心睿. 扶正化瘀方抗肝纤维化的网络多靶标作用机制研究[D]. 重庆: 中国人民解放军海军军医大学, 2019.
[33]	ZAHNG W, SHAO ML, ZHANG HC, et al. Expression of miR-122-related factors of liver fibrosis regulated by Fuzheng Huayu Tablet[J]. J Beijing Univ Chin Med, 2018, 41(1): 76-82. DOI: 10.3969/j.issn.1006-2157.2018.01.013. 张巍, 邵明亮, 张海丛, 等. 扶正化瘀片调节肝纤维化miR-122基因相关因子表达研究[J]. 北京中医药大学学报, 2018, 41(1): 76-82. DOI: 10.3969/j.issn.1006-2157.2018.01.013.
[34]	PAN Q, WANG YQ, LI GM, et al. Fuzheng Huayu recipe ameliorates liver fibrosis by restoring balance between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition in hepatic stellate cells[J]. Biomed Res Int, 2015, 2015: 935903. DOI: 10.1155/2015/935903.
[35]	HU XQ, SONG YN, WU R, et al. Metabolic mechanisms of Fuzheng-Huayu formula against liver fibrosis in rats[J]. J Ethnopharmacol, 2019, 238: 111888. DOI: 10.1016/j.jep.2019.111888.
[36]	WU M, XU LM. The regulatory effect of Fuzheng Huayu capsule on peripheral blood cytokines in hepatitis B-related cirrhosis patients with effectively antiviral therapy[J]. Chin Hepatol, 2017, 22(12): 1094-1097. DOI: 10.3969/j.issn.1008-1704.2017.12.008. 吴眉, 徐列明. 扶正化瘀胶囊对抗病毒有效的乙型肝炎肝硬化患者外周血细胞因子的调节[J]. 肝脏, 2017, 22(12): 1094-1097. DOI: 10.3969/j.issn.1008-1704.2017.12.008.
[37]	SHI K, LIU Y, WANG X, et al. Adjuvant Fuzheng Huayu capsule reduces the incidence of hepatocellular carcinoma in patients with hepatitis B-caused cirrhosis[J]. Evid Based Complement Alternat Med, 2020, 2020: 8826091. DOI: 10.1155/2020/8826091.
[38]	REN GP, ZHANG ZM, SUN LL, et al. The Effects of Fuzheng Huayu decoction on the cell cycle regulation in hepatic precancerosis induced by DEN in rats[J]. Clin Med Eng, 2011, 18(11): 1699-1700. DOI: 10.3969/j.issn.1674-4659.2011.11.1699. 任公平, 张忠敏, 孙琳林, 等. 扶正化瘀方对大鼠肝癌前病变细胞周期调控的影响[J]. 临床医学工程, 2011, 18(11): 1699-1700. DOI: 10.3969/j.issn.1674-4659.2011.11.1699.
[39]	LIU L, ZHANG HX, CHEN L, et al. Effect of Fuzheng Huayu decoction on the expression of MMP-3 and ESM-1 in patients with hepatocellular carcinoma[J]. China J Chin Med, 2019, 34(5): 1065-1069. DOI: 10.16368/j.issn.1674-8999.2019.05.252. 刘莲, 张红霞, 陈蕾, 等. 扶正化瘀方对肝癌患者MMP-3和ESM-1表达的影响[J]. 中医学报, 2019, 34(5): 1065-1069. DOI: 10.16368/j.issn.1674-8999.2019.05.252.
[40]	YUAN X. Fuzheng Huayu serum suppresses hepatic carcinoma cell Growth and Survival by targeting TGF-β1/smad Signaling[D]. Nanjing: Nanjing University of Chinese Medicine, 2017. 袁馨. 基于TGF-β1/smad信号通路探讨扶正化瘀含药血清抑制肝癌细胞发生、发展的研究[D]. 南京: 南京中医药大学, 2017.