四物汤对肝脏疾病的防治效应及其机制

管雅捷; 张丽慧; 刘素彤; 张琪振; 赵文霞; 刘鸣昊

doi:10.12449/JCH250734

四物汤对肝脏疾病的防治效应及其机制

DOI: 10.12449/JCH250734

管雅捷^{1, 2},
张丽慧¹,
刘素彤¹,
张琪振^{1, 2},
赵文霞¹,
刘鸣昊^1, , ,

1.
河南中医药大学第一附属医院脾胃肝胆科，郑州 450000
2.
河南中医药大学第一临床医学院，郑州 450046

基金项目:

国家自然科学基金 (81904154);

国家自然科学基金 (82205086);

河南省科技攻关计划 (242102310500);

河南省科技攻关计划 (232102310438);

河南省卫健委中医药传承创新专项 (2023ZXZX1162);

河南省卫生健康委员会 (2022JDZX114);

河南省“双一流”创建学科中医学科学研究专项 (HSRP-DFCTCM-2023-1-10);

河南省科技研发计划联合基金（优势学科培育类） (242301420096)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：管雅捷负责设计论文框架，起草论文；管雅捷、张琪振负责搜集相关文献；张丽慧、刘素彤负责论文修改；赵文霞、刘鸣昊负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
刘鸣昊， liumh015@163.com （ORCID： 0009-0001-7712-4605）

计量
- 文章访问数: 467
- HTML全文浏览量: 188
- PDF下载量: 41
- 被引次数: 0
出版历程
- 收稿日期: 2024-11-01
- 录用日期: 2025-02-25
- 出版日期: 2025-07-25

Effect of Siwu Decoction in the prevention and treatment of liver diseases and its mechanism

Yajie GUAN^{1, 2},
Lihui ZHANG¹,
Sutong LIU¹,
Qizhen ZHANG^{1, 2},
Wenxia ZHAO¹,
Minghao LIU^{1
, ,
,}

1.
Spleen，Stomach and Hepatobiliary Department，The First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450000，China
2.
The First Clinical Medical College of Henan University of Chinese Medicine，Zhengzhou 450046，China

Research funding:

National Natural Science Foundation of China (81904154);

National Natural Science Foundation of China (82205086);

Henan Province’s Science and Technology Assault Plan (242102310500);

Henan Province’s Science and Technology Assault Plan (232102310438);

Special Project on Inheritance and Innovation in Traditional Chinese Medicine by the Henan Health Commission (2023ZXZX1162);

Henan Health Commission (2022JDZX114);

Scientific Research Special Project under the “Double First-Class” Initiative for Traditional Chinese Medicine in Henan Province (HSRP-DFCTCM-2023-1-10);

Joint Fund for R&D in Science and Technology, Focusing on Advantage Discipline Cultivation Type, in Henan Province (242301420096)

More Information

Corresponding author: LIU Minghao， liumh015@163.com （ORCID： 0009-0001-7712-4605）

摘要

摘要: 四物汤作为补血活血的经典方剂，具有补血不留瘀、行血不伤正的特点，临床广泛应用于贫血、月经不调、痛经等血虚及血行不畅相关病症。肝主疏泄、藏血，其功能异常与多种急慢性肝损伤密切相关，四物汤通过补血活血、养血疏肝可有效改善肝脏稳态失衡。基于其精妙的组方配伍和多重药理机制，四物汤已成为改善肝脏微循环、促进肝细胞修复再生、减轻肝损伤的重要治疗方剂。本文系统综述四物汤对多种肝损伤（包括酒精性肝病、非酒精性脂肪性肝病、肝纤维化及肝硬化）的防治作用及机制，并针对当前问题与未来研究方向展开讨论。
- 肝疾病 /
- 四物汤 /
- 中药药理学
Abstract: Siwu Decoction is a classic formula for tonifying the blood and activating blood circulation and is characterized by its ability to tonify the blood without leaving stasis and promote blood circulation without harming the vital energy of the body. It is widely used in clinical practice for the treatment of various conditions related to blood deficiency and poor blood circulation， such as anemia， menstrual disorders， and dysmenorrhea. The liver is responsible for governing the free flow of Qi and storing blood， and abnormalities in liver function are associated with various acute and chronic liver injuries. Siwu Decoction can restore liver homeostasis by tonifying the blood， activating blood circulation， nourishing the blood， and soothing the liver. Based on its unique prescription formulation and multiple pharmacological mechanisms， Siwu Decoction has become an important prescription for enhancing liver microcirculation， facilitating hepatocyte repair and regeneration， and alleviating liver injury. This article reviews the effect and mechanism of Siwu Decoction in the prevention and treatment of various liver injuries （including alcoholic liver disease， nonalcoholic fatty liver disease， nonalcoholic fatty liver disease， liver fibrosis， and liver cirrhosis） and discusses existing problems and future research directions.
- Liver Diseases /
- Si Wu Decoction /
- Pharmacology （TCD）

HTML全文

表 1 四物汤防治肝脏疾病的药理机制

Table 1. The mechanism of Si-Wu-Tang on liver injury

药理机制	作用机制	参考文献
抑制细胞凋亡	下调促凋亡基因Bax、Fas	［2-3］
	下调caspase-3、caspase-8的表达	［2-3］
	下调p38 MAPK、mTOR的磷酸化	［7］
	下调JNK的磷酸化	［13］
抑制铁死亡	上调Nrf2、NQO1、HO-1的表达	［8］
	抑制ACSL4介导的花生四烯酸酯化	［18］
调节细胞自噬	下调p38 MAPK、mTOR磷酸化	［7］
抑制炎症反应	减少NET的形成，抑制STING的磷酸化	［9］
	下调TLR4、阻断JNK磷酸化	［13］
	下调IL-1β、OLR1表达	［27］
	下调IL-6、TNF-α炎症因子表达	［32］
抗氧化应激	上调Nrf2、HIF-1α蛋白表达	［22-23］
	促进AMPK的磷酸化	［32］
改善线粒体功能障碍	阻断mPTP的开放，减少mtDNA的释放	［15］
调节肠道菌群	调节肠道菌群组成，修复肠道屏障	［26］
调节胆汁酸稳态	激活FXR，调节胆汁酸组成	［26］
调节糖、脂质代谢	降低CEBPα的表达	［14］
	降低FAK和Src的磷酸化，抑制有氧糖酵解	［31］
抑制血管新生	降低VEGF和VEGFR2的蛋白表达，从而抑制血管新生	［6］
抑制细胞骨架重塑	下调lncRNA H19，抑制HSC骨架重塑	［29］
抗纤维化	抑制α-SMA、Ⅰ型胶原表达和HSC的活化	［25］
	抑制TGF-β表达	［32］
注：FAK，局部黏着斑激酶；Src，类固醇受体辅激活因子。

下载: 导出CSV

参考文献(37)

[1]	ZHANG YX, FANG XM. The pan-liver network theory: From traditional Chinese medicine to western medicine[J]. Chin J Physiol, 2023, 66( 6): 401- 436. DOI: 10.4103/cjop.CJOP-D-22-00131.
[2]	WANG ZY, GUO MZ, QUAN SJ. Influence of Siwu Decoction on hepatocyte apoptosis and related genes expression in mice with blood deficiency sydrome[J]. China J Tradit Chin Med Pharm, 2015, 30( 6): 2219- 2222. 王正引, 郭明章, 全世建. 四物汤对血虚证小鼠肝细胞凋亡以及凋亡相关基因表达的影响[J]. 中华中医药杂志, 2015, 30( 6): 2219- 2222.
[3]	WANG ZY, GUO MZ, CHEN Y. Effects of Siwu decoction on expression of Caspase3 and Caspase8 in hepatocytes of mice with blood deficiency syndrome[J]. J Shaanxi Univ Chin Med, 2017, 40( 6): 98- 102. DOI: 10.13424/j.cnki.jsctcm.2017.06.034. 王正引, 郭明章, 陈燕. 四物汤对血虚证小鼠肝细胞凋亡相关分子Caspase3及Caspase8表达的影响[J]. 陕西中医药大学学报, 2017, 40( 6): 98- 102. DOI: 10.13424/j.cnki.jsctcm.2017.06.034.
[4]	GONG WJ, WO XD, LU DZ, et al. Effect of Siwu decoction on liver mitochondrial proteome of blood deficiency model rats[J]. J Tradit Chin Med, 2010, 51( 2): 160- 163. DOI: 10.13288/j.11-2166/r.2010.02.038. 龚文君, 沃兴德, 卢德赵, 等. 四物汤对血虚证模型大鼠肝线粒体蛋白质组的影响[J]. 中医杂志, 2010, 51( 2): 160- 163. DOI: 10.13288/j.11-2166/r.2010.02.038.
[5]	ZHOU LJ, HE Y. Effects of Siwu Tang on the hemorheology in acute blood-stasis model rats[J]. Pharmacol Clin Chin Mater Med, 2015, 31( 4): 3- 6. DOI: 10.13412/j.cnki.zyyl.2015.04.002. 周莉江, 何瑶. 四物汤对急性血瘀模型大鼠血液流变性作用的研究[J]. 中药药理与临床, 2015, 31( 4): 3- 6. DOI: 10.13412/j.cnki.zyyl.2015.04.002.
[6]	WANG L, LI JN, YANG Y, et al. Effect and mechanism of individual components of Siwu Tang in treatment of cholestatic liver injury based on network pharmacology and experimental validation in vivo[J]. Chin Tradit Herb Drugs, 2024, 55( 5): 1553- 1566. DOI: 10.7501/j.issn.0253-2670.2024.05.014. 汪乐, 李佳楠, 杨洋, 等. 基于网络药理学整合体内实验探究四物汤单味药组分治疗胆汁淤积性肝损伤的作用与机制[J]. 中草药, 2024, 55( 5): 1553- 1566. DOI: 10.7501/j.issn.0253-2670.2024.05.014.
[7]	DENG XY, LI YB, CHEN Y, et al. Paeoniflorin protects hepatocytes from APAP-induced damage through launching autophagy via the MAPK/mTOR signaling pathway[J]. Cell Mol Biol Lett, 2024, 29( 1): 119. DOI: 10.1186/s11658-024-00631-4.
[8]	TANG WC, HE Q, LI JF, et al. Ligustrazine alleviates acetaminophen-induced liver injury by inhibiting inflammatory response and ferroptosis[J]. World Chin Med, 2023, 18( 24): 3512- 3517. DOI: 10.3969/j.issn.1673-7202.2023.24.006. 唐文诚, 何清, 李俊峰, 等. 川芎嗪通过抑制炎症反应和铁死亡减轻对乙酰氨基酚所致肝损伤[J]. 世界中医药, 2023, 18( 24): 3512- 3517. DOI: 10.3969/j.issn.1673-7202.2023.24.006.
[9]	LIU YY, QIN XY, LEI ZL, et al. Tetramethylpyrazine inhibits neutrophil extracellular traps formation and alleviates hepatic ischemia/reperfusion injury in rat liver transplantation[J]. Exp Cell Res, 2021, 406( 1): 112719. DOI: 10.1016/j.yexcr.2021.112719.
[10]	YOUNOSSI ZM, GOLABI P, PAIK JM, et al. The global epidemiology of nonalcoholic fatty liver disease(NAFLD) and nonalcoholic steatohepatitis(NASH): A systematic review[J]. Hepatology, 2023, 77( 4): 1335- 1347. DOI: 10.1097/HEP.0000000000000004.
[11]	ZHAO WX, XU EP, WANG XB, et al. Diagnosis and treatment guideline for chinese medicine on non-alcoholic steatohepatitis[J]. J Clin Hepatol, 2023, 39( 5): 1041- 1048. DOI: 10.3969/j.issn.1001-5256.2023.05.007. 赵文霞, 许二平, 王宪波, 等. 非酒精性脂肪性肝炎中医诊疗指南[J]. 临床肝胆病杂志, 2023, 39( 5): 1041- 1048. DOI: 10.3969/j.issn.1001-5256.2023.05.007.
[12]	CAI XQ, CAI YY, XIE HD. Clinical observation of 124 cases of nonalcoholic fatty liver disease treated with Erchen Siwu Decoction[J]. World Chin Med, 2017, 12( 2): 285- 288. DOI: 10.3969/j.issn.1673-7202.2017.02.012. 蔡小旗, 蔡媛媛, 谢红丹. 加减二陈四物汤治疗非酒精性脂肪肝124例临床观察[J]. 世界中医药, 2017, 12( 2): 285- 288. DOI: 10.3969/j.issn.1673-7202.2017.02.012.
[13]	ZHANG YX, ZHOU G, CHEN ZF, et al. Si-wu-Tang alleviates nonalcoholic fatty liver disease via blocking TLR4-JNK and caspase-8-GSDMD signaling pathways[J]. Evid Based Complement Alternat Med, 2020, 2020: 8786424. DOI: 10.1155/2020/8786424.
[14]	AI ZL, ZHANG X, WANG HY, et al. Mechanism of Siwu decoction in reducing body weight and lipid via lipidomics and transcriptomics[J]. Chin Arch Tradit Chin Med, 2023, 38( 5): 2257- 2263. 艾梓黎, 张娴, 王海燕, 等. 基于脂质组学和转录组学探讨四物汤减重降脂的作用机制[J]. 中华中医药杂志, 2023, 38( 5): 2257- 2263.
[15]	MA Z, XIE KH, XUE XY, et al. Si-Wu-Tang attenuates hepatocyte PANoptosis and M1 polarization of macrophages in non-alcoholic fatty liver disease by influencing the intercellular transfer of mtDNA[J]. J Ethnopharmacol, 2024, 328: 118057. DOI: 10.1016/j.jep.2024.118057.
[16]	WANG JH, LIANG DH. Mechanism study of Siwu decoction on non-alcoholic fatty liver in mice[J]. Hebei J Tradit Chin Med, 2017, 39( 3): 420- 423, 438. DOI: 10.3969/j.issn.1002-2619.2017.03.026. 王家华, 梁丹红. 四物汤对非酒精性脂肪性肝病小鼠的作用机制研究[J]. 河北中医, 2017, 39( 3): 420- 423, 438. DOI: 10.3969/j.issn.1002-2619.2017.03.026.
[17]	CHIU HF, WU YH, SHEN YC, et al. Antioxidant and physiological effects of Si-Wu-Tang on skin and liver: A randomized, double-blind, placebo-controlled clinical trial[J]. Chin Med, 2016, 11: 30. DOI: 10.1186/s13020-016-0102-0.
[18]	XUE XY, WANG L, WU RY, et al. Si-Wu-Tang alleviates metabolic dysfunction-associated fatty liver disease by inhibiting ACSL4-mediated arachidonic acid metabolism and ferroptosis in MCD diet-fed mice[J]. Chin Med, 2024, 19( 1): 79. DOI: 10.1186/s13020-024-00953-7.
[19]	ZHANG YX, BI MM, CHEN ZF, et al. Hydrogen gas alleviates acute alcohol-induced liver injury by inhibiting JNK activation[J]. Exp Ther Med, 2021, 21( 5): 453. DOI: 10.3892/etm.2021.9884.
[20]	BAI YF, LI XJ, LI YG, et al. Protective effect of Siwu decoction on alcoholic hepatic injury in mice[J]. Chin J Comp Med, 2015, 25( 2): 11- 14, 81. DOI: 10.3969.j.issn.1671.7856.2015.002.003. 白云峰, 李晓娟, 李永纲, 等. 四物汤干预减轻乙醇对小鼠肝脏的损伤作用[J]. 中国比较医学杂志, 2015, 25( 2): 11- 14, 81. DOI: 10.3969.j.issn.1671.7856.2015.002.003.
[21]	JIA L, WANG LL, MENG L, et al. Effects of Baishao on liver Yin deficiency pattern in alcoholic liver injury and its mechanism[J]. J Beijing Univ Tradit Chin Med, 2020, 43( 3): 203- 211. DOI: 10.3969/j.issn.1006-2157.2020.03.005. 贾岚, 王蕾蕾, 孟靓, 等. 白芍对酒精性肝损伤肝阴虚证的保护功效和机制[J]. 北京中医药大学学报, 2020, 43( 3): 203- 211. DOI: 10.3969/j.issn.1006-2157.2020.03.005.
[22]	LU CF, XU WX, SHAO JJ, et al. Nrf2 activation is required for ligustrazine to inhibit hepatic steatosis in alcohol-preferring mice and hepatocytes[J]. Toxicol Sci, 2017, 155( 2): 432- 443. DOI: 10.1093/toxsci/kfw228.
[23]	CAO P, ZHANG Y, WANG HX, et al. Preventive effect of Angelica sinensis polysaccharide on acute alcoholic liver injury in mice and its influence on HIF-1α protein[J]. China J Tradit Chin Med Pharm, 2021, 36( 6): 3628- 3631. 曹鹏, 张玉, 汪汉香, 等. 当归多糖对小鼠急性酒精性肝病的预防作用及对HIF-1α蛋白的影响[J]. 中华中医药杂志, 2021, 36( 6): 3628- 3631.
[24]	WANG S. Effect of Taohong Siwu decoction combined with interferon on liver fibrosis in patients with hepatitis B virus infection[J]. Pract Pharm Clin Remedies, 2014, 17( 5): 655- 657. DOI: 10.14053/j.cnki.ppcr.2014.05.007. 王舜. 桃红四物汤联合干扰素对乙型肝炎病毒感染患者肝纤维化的影响[J]. 实用药物与临床, 2014, 17( 5): 655- 657. DOI: 10.14053/j.cnki.ppcr.2014.05.007.
[25]	LIU XL, YANG GY, ZHANG W, et al. Therapeutic effect of Taohong Siwu decoction on a mouse model of carbon tetrachloride-induced liver fibrosis and its mechanism[J]. J Clin Hepatol, 2021, 37( 11): 2563- 2568. DOI: 10.3969/j.issn.1001-5256.2021.11.016. 刘旭凌, 杨广越, 张玮, 等. 桃红四物汤对CCl₄诱导肝纤维化小鼠模型的干预作用及其机制[J]. 临床肝胆病杂志, 2021, 37( 11): 2563- 2568. DOI: 10.3969/j.issn.1001-5256.2021.11.016.
[26]	XUE XY, WU JZ, DING MN, et al. Si-Wu-Tang ameliorates fibrotic liver injury via modulating intestinal microbiota and bile acid homeostasis[J]. Chin Med, 2021, 16( 1): 112. DOI: 10.1186/s13020-021-00524-0.
[27]	WANG L, QU JR, LI JN, et al. Si-Wu-Tang improves liver fibrosis by restoring liver sinusoidal endothelial cell functionality and reducing communication with hepatic stellate cells[J]. Chin Med, 2024, 19( 1): 179. DOI: 10.1186/s13020-024-01038-1.
[28]	QU JR, XUE XY, WANG ZX, et al. Si-Wu-Tang attenuates liver fibrosis via regulating lncRNA H19-dependent pathways involving cytoskeleton remodeling and ECM deposition[J]. Chin J Nat Med, 2024, 22( 1): 31- 46. DOI: 10.1016/S1875-5364(24)60560-1.
[29]	MA Z, XUE XY, BAI JZ, et al. Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment[J]. Biomed Pharmacother, 2022, 155: 113834. DOI: 10.1016/j.biopha.2022.113834.
[30]	WANG T, HE L, WANG SX, et al. Association between nonalcoholic steatohepatitis and high serum ferritin levels in type 2 diabetes mellitus[J]. Rev Assoc Med Bras(1992), 2024, 70( 7): e20231405. DOI: 10.1590/1806-9282.20231405.
[31]	ZHANG QX, RAN T, LI SL, et al. Catalpol ameliorates liver fibrosis via inhibiting aerobic glycolysis by EphA2/FAK/Src signaling pathway[J]. Phytomedicine, 2024, 135: 156047. DOI: 10.1016/j.phymed.2024.156047.
[32]	WU JZ, XUE XY, FAN GF, et al. Ferulic acid ameliorates hepatic inflammation and fibrotic liver injury by inhibiting PTP1B activity and subsequent promoting AMPK phosphorylation[J]. Front Pharmacol, 2021, 12: 754976. DOI: 10.3389/fphar.2021.754976.
[33]	LI L, WANG L. Clinical observation on Siwu decoction in the treatment of decompensated liver cirrhosis[J]. Chin Med Mod Distance Educ China, 2021, 19( 12): 107- 109. DOI: 10.3969/j.issn.1672-2779.2021.12.040. 李玲, 王龙. 四物汤治疗失代偿期肝硬化临床观察[J]. 中国中医药现代远程教育, 2021, 19( 12): 107- 109. DOI: 10.3969/j.issn.1672-2779.2021.12.040.
[34]	CHE JY, LU WT, HE J, et al. Clinical observation on Jiawei Siwu decoction in preventing the adverse reactions caused by PEG-IFNα-2a in the treatment of chronic hepatitis B[J]. J Shandong Univ Tradit Chin Med, 2017, 41( 5): 432- 433, 444. DOI: 10.16294/j.cnki.1007-659x.2017.05.012. 车军勇, 陆玮婷, 何晶, 等. 加味四物汤对PEG-IFNα-2a治疗慢性乙型病毒性肝炎常见不良反应的干预作用[J]. 山东中医药大学学报, 2017, 41( 5): 432- 433, 444. DOI: 10.16294/j.cnki.1007-659x.2017.05.012.
[35]	HE JY, CAO XY, YE MQ, et al. Clinical study on the therapeutic effect of Wuling powder and Taohong Siwu decoction on cirrhotic ascites of syndrome of static blood blocking collaterals[J]. Chin J Integr Tradit West Med Liver Dis, 2022, 32( 9): 803- 806. DOI: 10.3969/j.issn.1005-0264.2022.09.009. 何瑾瑜, 曹雪艳, 叶苗青, 等. 五苓散联合桃红四物汤治疗瘀血阻络型肝硬化腹水的临床研究[J]. 中西医结合肝病杂志, 2022, 32( 9): 803- 806. DOI: 10.3969/j.issn.1005-0264.2022.09.009.
[36]	YAO N, WANG YH, WANG X, et al. Effects of angelicae sinensis Radix-paeoniae Radix alba combined with BM-MSCs transplantation on liver inflammation and hepatocytes regeneration in mice with NASH related cirrhosis[J]. Chin J Inf Tradit Chin Med, 2024, 31( 11): 129- 135. DOI: 10.19879/j.cnki.1005-5304.202404324. 姚凝, 王钰涵, 王昕, 等. 当归-白芍联合BM-MSCs移植对NASH相关肝硬化小鼠肝脏炎症及肝细胞再生的影响[J]. 中国中医药信息杂志, 2024, 31( 11): 129- 135. DOI: 10.19879/j.cnki.1005-5304.202404324.
[37]	LI D, RUI YX, GUO SD, et al. Ferulic acid: A review of its pharmacology, pharmacokinetics and derivatives[J]. Life Sci, 2021, 284: 119921. DOI: 10.1016/j.lfs.2021.119921.