1.上海中医药大学附属曙光医院,上海市中医药研究院肝病研究所,肝肾疾病病证教育部重点实验室,上海市中医临床重点实验室(上海 201203)
2.上海中医药大学交叉科学研究院(上海 201203)
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陈佳美,慕永平,刘平.“病⁃方(效)⁃证”的研究实践与创新发展(二)[J].上海中医药大学学报,2023,37(02):1-6.
CHEN Jiamei,MU Yongping,LIU Ping.Research practice and innovative development of “disease⁃formula (effect)⁃syndrome” (Ⅱ) —Analysis on pathological basis of formula and syndrome of Yiguanjian in treatment of liver cirrhosis[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2023,37(02):1-6.
陈佳美,慕永平,刘平.“病⁃方(效)⁃证”的研究实践与创新发展(二)[J].上海中医药大学学报,2023,37(02):1-6. DOI: 10.16306/j.1008-861x.2023.02.001.
CHEN Jiamei,MU Yongping,LIU Ping.Research practice and innovative development of “disease⁃formula (effect)⁃syndrome” (Ⅱ) —Analysis on pathological basis of formula and syndrome of Yiguanjian in treatment of liver cirrhosis[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2023,37(02):1-6. DOI: 10.16306/j.1008-861x.2023.02.001.
基于肝炎后肝硬化气虚血瘀的核心病机及肝肾阴虚、湿热内蕴的主要证候病机,采用不同功效中医古典方剂进行肝硬化多模型的疗效比较研究,明确滋肾养肝的一贯煎对肝细胞损伤为主的肝硬化模型有突出的作用。临床研究证实,一贯煎可显著改善失代偿期乙肝肝硬化肝肾阴虚为主证患者的Child-Pugh评分;深入研究表明,一贯煎治疗肝硬化主要机制在于改善肝实质细胞衰减,调控干细胞分化促进肝再生,改善肝组织缺氧状态,抑制肝窦内皮细胞损伤,血管新生以及改善炎症微环境等。基于“病-方(效)-证”相关理论,认为肝硬化肝肾阴虚证的关键病理学基础与肝实质细胞衰减、肝再生障碍、肝组织缺氧、肝窦内皮损伤和血管新生,以及与巨噬细胞为主的炎症微环境病变有关。提示着力加强方证病理生物学基础研究可能成为中医药治疗慢性难治性疾病的突破口。
Based on the core pathogenesis of blood stasis due to qi deficiency in post-hepatitis cirrhosis and the main syndrome pathogenesis of yin deficiency of the liver and kidney, and damp-heat brewing internally, a comparative study on the efficacy of multiple models of cirrhosis with different efficacy of traditional Chinese medicine (TCM) formulas, to demonstrate that the kidney and liver nourishing formula Yiguanjian had a prominent effect on hepatocyte damage dominated liver cirrhosis model. Yiguanjian can significantly improve the Child-Pugh score of patients with yin deficiency of the liver and kidney in decompensated hepatitis B cirrhosis. In-depth studies have showed that the main mechanisms of Yiguanjian in the treatment of cirrhosis are to improve the attenuation of hepatic parenchymal cells, regulate stem cell differentiation to promote liver regeneration, improve the hypoxia state of liver tissue, inhibit the damage of hepatic sinusoidal endothelial cells and angiogenesis, and improve the inflammatory microenvironment. Based on the theory of “disease-formula (effect)-syndrome”, it is believed that the key pathological basis of liver and kidney yin deficiency syndrome in cirrhosis is related to hepatic parenchymal cell attenuation, liver regeneration disorder, liver tissue hypoxia, hepatic sinus endothelial injury and angiogenesis, as well as macrophage-dominated inflammatory microenvironment lesions. It is suggested that strengthening the basic research of pathobiology of formula and syndrome may be the breakthrough of TCM treatment of chronic refractory diseases.
证候病机方证病理学肝硬化一贯煎肝细胞衰减肝再生肝窦内皮细胞
syndrome pathogenesispathology of formula and syndromeliver cirrhosisYiguanjianhepatocyte attenuationliver regenerationhepatic sinusoidal endothelial cells
慕永平,刘平. “病-方(效)-证”的研究实践与创新发展(一)——黄芪汤治疗肝硬化的方证病理学基础探析[J]. 上海中医药大学学报,2022, 36(5): 6-11,33.
MU Y P,LIU P. Research practice and innovative development of “disease-formula(effect)-syndrome” (I) —analysis on pathological basis of formula and syndrome of Huangqi Decoction in treatment of liver cirrhosis[J]. Journal of Shanghai University of Traditional Chinese Medicine, 2022, 36(5): 6-11,33.
周扬,胡鑫才,张华,等. 493例慢性肝炎及肝硬化患者中医证候研究[J]. 中华中医药杂志,2014, 29(12): 3798-801.
ZHOU Y, HU X C, ZHANG H, et al. TCM syndrome study on 493 patients with chronic hepatitis and hepatic cirrhosis[J]. China Journal of Traditional Chinese Medicine and Pharmacy, 2014, 29(12): 3798-801.
张琴,邱宏,王磊,等. 355例肝炎后肝硬化患中医证候与生物学指标的关系[J]. 中西医结合学报,2007, 5(2): 130-133.
ZHANG Q, QIU H, WANG L, et al. Correlation between syndromes of posthepatitic cirrhosis and biological parameters:a report of 355cases[J]. Journal of Chinese Integrative Medicine, 2007, 5(2): 130-133.
袁继丽,张华,王磊,等. 乙型肝炎后肝硬化患者中医证候要素的生物化学特征[J]. 中西医结合学报,2011, 9(4): 374-381.
YUAN J L, ZHANG H, WANG L, et al. Biochemical characteristics of traditional Chinese medicine syndromes and their elements in patients with hepatitis B cirrhosis[J]. Journal of Chinese Integrative Medicine, 2011, 9(4): 374-381.
张琴,刘平,陈慧芬,等. 肝炎后肝硬化中医证候特点的临床调查研究[J]. 中西医结合学报,2003, 1(2): 108-112.
ZHANG Q,LIU P,CHEN H F,et al.Clinical investigation on characteristics of traditional Chinese medical syndrome of hepatocirrhosis[J]. Journal of Chinese Integrative Medicine, 2003, 1(2): 108-112.
CHEN L, ZHAO C Q, YAO W L, et al. Efficacy and Safety of Yanggan Jian in Hepatitis B Virus-related Decompensated Cirrhosis: A Randomized, Double-blind, Controlled Trial[J]. J Clin Transl Hepatol, 2023, 11(1): 136-143.
慕永平,刘平,龙爱华,等. CCl4大鼠肝硬化成型阶段中医方证病机的研究[J]. 中国中西医结合杂志,2006, 26(4): 344-347.
MU Y P, LIU P, LONG A H, et al. Study on Pathogenesis of CCl4 Induced Cirrhosis Formation in Rats Based on the Recipe Used[J]. Chinese Journal of Integrated Traditional and Western Medicine, 2006, 26(4): 344-347.
慕永平,刘平,王磊,等. 一贯煎影响CCl4大鼠肝硬化形成期肝组织基因表达谱的效应机制研究[J]. 世界科学技术-中医药现代化,2007, 9(3): 43-54.
MU Y P,LIU P,WANG L,et al.Hepatic Gene Expresion Analysisof Carbon Tetrachloride Induced Rat Cirhosis Identifies Distinct Efectsof Yiguanjian Decoction[J]. Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology, 2007, 9(3): 43-54.
ALEGRE F, PELEGRIN P, FELDSTEIN A E. Inflammasomes in Liver Fibrosis[J]. Semin Liver Dis, 2017, 37(2): 119-127.
LEMMER P, POSPIECH J C, CANBAY A. Liver failure-future challenges and remaining questions[J]. Ann Transl Med, 2021, 9(8): 734.
FRIEDMAN S L,PINZANI M. Hepatic fibrosis 2022: Unmet needs and a blueprint for the future[J]. Hepatology, 2022, 75(2): 473-488.
MU Y P, LIU P, DU G L, et al. Action mechanism of Yi Guan Jian Decoction on CCl4 induced cirrhosis in rats [J]. J Ethnopharmacol, 2009, 121(1): 35-42.
申定珠,陶庆,都金星,等. 基于差异蛋白质组学解析一贯煎对大鼠肝硬化形成的影响[J]. 中西医结合学报,2010, 8(2): 158-167.
SHEN D Z,TAO Q,DOU J X,et al.Effects of Yiguanjian Decoction on liver cirrhosis formation: a differential proteomics study in rats[J]. Journal of Chinese Integrative Medicine, 2010, 8(2): 158-167.
闫晓风,赵培,叶杰,等. 一贯煎通过上调自噬抑制H2O2诱导的肝细胞损伤[J]. 中华中医药杂志,2017, 32(2): 564-569.
YAN X F, ZHAO P, YE J, et al. Yiguan Decoction inhibits H2O2-induced hepatocyte injury via upregulating the autophagy[J]. China Journal of Traditional Chinese Medicine and Pharmacy,2017, 32(2): 564-569.
MO Z Z, LIN Z X, SU Z R, et al. Angelica sinensis Supercritical Fluid CO2 Extract Attenuates D-Galactose-Induced Liver and Kidney Impairment in Mice by Suppressing Oxidative Stress and Inflammation[J]. J Med Food, 2018, 21(9): 887-898.
曹健美,陶庆,慕永平,等. 一贯煎对CCl4诱导肝纤维化大鼠肝细胞凋亡及其调控基因表达的影响[J]. 上海中医药大学学报,2012, 26(5): 70-75.
CAO J M, TAO Q, MU Y P, et al. Effect of “Yiguan Decoction” on Hepatocellular Apoptosis and Underlying Gene Expression inCCl4-induced Hepatic Fibrosis[J]. Journal of Shanghai University of Traditional Chinese Medicine, 2012, 26(5): 70-75.
WANG J,SUN M,LIU W,et al. Stem Cell-Based Therapies for Liver Diseases: An Overview and Update [J]. Tissue Eng Regen Med, 2019, 16(2): 107-118.
SATTWIKA P D,INDRARTI F,BAYUPURNAMA P. Clinical Application of Stem Cell Therapy for Liver Cirrhosis: Progress, Pitfalls, and Prospects[J]. Acta Med Indones,2021, 53(4): 473-480.
WOO D H, KIM S K, LIM H J, et al. Direct and indirect contribution of human embryonic stem cell-derived hepatocyte-like cells to liver repair in mice[J]. Gastroenterology, 2012, 142(3): 602-611.
CHEN J, ZHANG X, XU Y, et al. Hepatic Progenitor Cells Contribute to the Progression of 2-Acetylaminofluorene/Carbon Tetrachloride-Induced Cirrhosis via the Non-Canonical Wnt Pathway[J]. PLoS One, 2015, 10(6): e0130310.
ZHANG X, DU G, XU Y, et al. Inhibition of notch signaling pathway prevents cholestatic liver fibrosis by decreasing the differentiation of hepatic progenitor cells into cholangiocytes [J]. Lab Invest, 2016, 96(3): 350-360.
QIN L, LIU N, BAO C L, et al. Mesenchymal stem cells in fibrotic diseases-the two sides of the same coin [J]. Acta Pharmacol Sin,2022, 27: 1-20.
平键,陈红云,周扬,等. 一贯煎诱导骨髓间充质干细胞分化为肝细胞样细胞的实验研究[J]. 中国中西医结合杂志,2014, 34(3): 348-354.
PING J, CHEN Y H, ZHOU Y, et al.Effect of Yiguan Decoction on Differentiation of Bone Marrow Mesenchymal Stem Cells into Hepatocyte- like Cells: an Experimental Research[J]. Chinese Journal of Integrated Traditional and Western Medicine, 2014, 34(3): 348-354.
闫晓风,叶䁎杰,刘会洋,等. 骨髓间充质干细胞向肌成纤维细胞转化及一贯煎的影响[J]. 中国实验方剂学杂志,2011, 17(22): 123-126.
YAN X F, YE T J, LIU H Y, et al.Differerntiation of Mesenchymal Stem Cells into Myofibroblasts and the Impact of Yiguanjian[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2011, 17(22): 123-126.
XIANG Y, PANG B Y, ZHANG Y, et al. Effect of Yi Guan Jian decoction on differentiation of bone marrow mesenchymalstem cells into hepatocyte-like cells in dimethylnitrosamine-induced liver cirrhosis in mice[J]. Mol Med Rep, 2017, 15(2): 613-626.
李汶航,张睿,崔欣怡,等. 一贯煎联合骨髓间充质干细胞调控RhoA/ROCK1通路抑制大鼠肝纤维化的实验研究[J]. 世界中医药,2022, 17(18): 2563-2568.
LI W H, ZHANG R, CUI X Y, et al.Yiguanjian Combined with Bone Marrow Mesenchymal Stem Cells Treats Liver Fibrosis in Rats via RhoA/ROCK1 Signaling Pathway[J].World Chinese Medicine, 2022, 17(18): 2563-2568.
乔天阳,刘文兰,王文娟,等. 一贯煎及骨髓间充质干细胞对肝纤维化大鼠阴虚证表征影响的实验研究[J]. 环球中医药,2017, 10(4): 419-424.
QIAO T Y, LIU W L, WANG W J, et al. Experimental study on the effect of Yiguanjian and bone marrow mesenchymal stem cells on the expression of yin deficiency syndrome in rats with hepatic fibrosis[J]. Globel Traditional Chinese Medicine, 2017, 10(4): 419-424.
WANG X L, JIA D W, LIU H Y, et al. Effect of Yiguanjian decoction on cell differentiation and proliferation in CCl4-treated mice[J]. World J Gastroenterol, 201218(25): 3235-3249.
XU Y, FAN WW, XU W, et al. Yiguanjian decoction enhances fetal liver stem/progenitor cell-mediated repair of liver cirrhosis through regulation of macrophage activation state[J]. World J Gastroenterol, 2018, 24(42): 4759-7472.
管艳,张辉,张玮,等. 慢性乙型病毒性肝炎肝肾阴虚证与湿热蕴结证患者外周血的差异基因表达谱分析[J]. 中西医结合学报,2012, 10(7): 751-756.
GUAN Y, ZHANG H, ZHANG W, et al. Analysis of diferential gene expression profile in peripheral blood of patients with chronic hepatitis B and syndromes of dual deficiency of liver and kidney yin and accumulation of dampness heat[J].Journal of Chinese Integrative Medicine, 2012, 10(7): 751-756.
GRACIA-SANCHO J, CAPARROS E, FERNANDEZ-IGLESIAS A, et al.Role of liver sinusoidal endothelial cells in liver diseases[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(6): 411-431.
GREUTER T, SHAH V H. Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights[J]. J Gastroenterol, 2016, 51(6): 511-519.
NATH B, SZABO G. Hypoxia and hypoxia inducible factors: diverse roles in liver diseases[J]. Hepatology, 2012, 55(2): 622-633.
ZHOU Y N, MU Y P, FU W W, et al. Yiguanjian decoction and its ingredients inhibit angiogenesis in carbon tetrachloride-induced cirrhosis mice[J]. BMC Complement Altern Med, 2015, 15: 342.
XU Y, XU W, LIU W, et al. Yiguanjian decoction inhibits macrophage M1 polarization and attenuates hepatic fibrosis induced by CCl4/2-AAF[J]. Pharm Biol, 2021, 59(1): 1150-1160.
陶庆,王晓柠,慕永平,等. 四氯化碳诱导大鼠肝纤维化脂质过氧化相关蛋白表达的动态变化及一贯煎的干预效应[J]. 中华肝脏病杂志,2012, 20(2): 116-121.
TAO Q, WANG X N, MU Y P, et al. Dynamic change of lipid peroxidation-related protein expression and the intervention effects of Yiguanjian Decoction in a rat model of CCl4-induced liver fibrosis[J]. Chinese Journal of Hepatology, 2012, 20(2): 116-121.
蔡智刚,唐新征,张毅. MCP-1/CCR2在老年高血压不同证型中的表达[J]. 临床合理用药杂志,2013, 6(8): 88-89.
CAI Z G, TANG X Z, ZHANG Y. Expression of MCP-1/CCR2 in different syndromes of senile hypertension[J]. Journal of Clinical Rational Drug Use, 2013, 6(8): 88-89.
李培. 代谢综合征中医分型中炎症因子水平的研究[J]. 中医学报,2013, 23(9): 1359-1360.
LI P. Study on the Inflammatory Factor Level of Traditional Chinese Medicine Typing of Metabolic Syndrome[J]. Acta Chinese Medicine, 2013, 23(9): 1359-1360.
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