基于中医阴阳学说探讨巨噬细胞极化在肝纤维化中的作用
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摘要
作为肝脏疾病的早期可逆转阶段,肝纤维化日益受到学者的关注。巨噬细胞极化是指巨噬细胞针对微环境刺激所产生的应答状态,其极化状态分为M1型和M2型两类,二者在肝纤维化进程的不同阶段发挥拮抗作用,与中医学说中的阴阳对立制约、转化、自和与平衡有着相似的内涵。尝试从中医阴阳学说探讨巨噬细胞极化在肝纤维化中的作用,提出当M1型巨噬细胞效应过强时,可治以滋阴养血、柔肝清火,方选一贯煎等;当M2型巨噬细胞效应过强时,可治以理气暖肝,方选暖肝煎等。
Liver fibrosis,as the early reversible phase of liver disease,is increasingly concerned by scholars.Macrophage polarization refers to the response state produced by macrophages in response to microenvironmental stimulation.The polarization state is divided into M1 and M2 types,which play an antagonistic role in different stages of liver fibrosis.It has similar connotations to mutually opposing and constraining,transformation,self-harmony and balance in the yin and yang theory of traditional Chinese medicine.This paper attempted to explore the role of macrophage polarization in liver fibrosis from the yin and yang theory of traditional Chinese medicine,proposing that when the effect of M1 macrophages is too strong,it can be treated with nourishing yin and nourishing blood,softening the liver and clearing fire,and selecting Yiguan Decoction(一贯煎);When the effect of M2 macrophage is too strong,it can be treated with regulating qi and warming the liver,and selecting Nuangan Decoction(暖肝煎).
Liver fibrosis,as the early reversible phase of liver disease,is increasingly concerned by scholars.Macrophage polarization refers to the response state produced by macrophages in response to microenvironmental stimulation.The polarization state is divided into M1 and M2 types,which play an antagonistic role in different stages of liver fibrosis.It has similar connotations to mutually opposing and constraining,transformation,self-harmony and balance in the yin and yang theory of traditional Chinese medicine.This paper attempted to explore the role of macrophage polarization in liver fibrosis from the yin and yang theory of traditional Chinese medicine,proposing that when the effect of M1 macrophages is too strong,it can be treated with nourishing yin and nourishing blood,softening the liver and clearing fire,and selecting Yiguan Decoction(一贯煎);When the effect of M2 macrophage is too strong,it can be treated with regulating qi and warming the liver,and selecting Nuangan Decoction(暖肝煎).
引文
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[24]JOHNSON A,DIPIETRO LA.Apoptosis and angiogenesis:an evolving mechanism for fibrosis[J].FASEB J,2013,27(10):3893-3901.
[25]WIGHT TN,POTTER-PERIGO S.The extracellular matrix:an active or passive player in fibrosis?[J].Am JPhysiol Gastrointest Liver Physiol,2011,301(6):G950-G955.
[26]GOERDT S,POLITZ O,SCHLEDZEWSKI K,et al.Alternative versus classical activation of macrophages[J].Pathobiology,1999,67(5/6):222-226.
[27]PRADERE JP,KLUWE J,DE MINICIS S,et al.Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in mice[J].Hepatology,2013,58(4):1461-1473.
[28]BENOIT M,DESNUES B,MEGE JL.Macrophage polarization in bacterial infections[J].J Immunol,2008,181(6):3733-3739.
[29]NOEL W,RAES G,HASSANZADEH GG,et al.Alternatively activated macrophages during parasite infections[J].Trends Parasitol,2004,20(3):126-133.
[30]ABRAMSON SL,GALLIN JI.IL-4 inhibits superoxide production by human mononuclear phagocytes[J].JImmunol,1990,144(2):625-630.
[31]MROWIETZ U,SEIFERT O.Keloid scarring:new treatments ahead[J].Actas Dermosifiliogr,2009,100 Suppl2:75-83.
[32]HUNG K,LEE T,CHOU W,et al.Interleukin-10 gene therapy reverses thioacetamide-induced liver fibrosis in mice[J].Biochem Biophy Res Commun,2005,336(1):324-331.
[33]PESCE JT,RAMALINGAM TR,MENTINK-KANE MM,et al.Arginase-1-expressing macrophages suppress Th2cytokine-driven inflammation and fibrosis[J].PLo SPathog,2009,5(4):e1000371.
[34]BAI L,FU L,LI L,et al.Cellular Mechanisms of Hepatoprotection Mediated by M2-Like Macrophages[J].Med Sci Monit,2018,24:2675-2682.doi:10.12659/MSM.907222.
[35]PELLICORO A,RAMACHANDRAN P,IREDALE JP,et al.Liver fibrosis and repair:immune regulation of wound healing in a solid organ[J].Nat Rev Immunol,2014,14(3):181-194.
[36]DULTZ G,GERBER L,FARNIK H,et al.Soluble CD163 is an indicator of liver inflammation and fibrosis in patients chronically infected with the hepatitis B virus[J].J Viral Hepat,2015,22(4):427-432.
[37]宛硕,黄艳,陈庭金,等.巨噬细胞极化的研究进展[J].中国病原生物学杂志,2015,10(11):1051-1054.
[38]高晓宇,张哲,王洋,等.基于脾虚生痰理论探讨巨噬细胞自噬与动脉粥样硬化的关系[J].中医杂志,2017,58(22):1902-1905.
[39]蒙玉娇,何秀娟,林燕,等.回阳生肌膏拆方对慢性皮肤溃疡模型小鼠疮面愈合及疮面巨噬细胞表型转化的影响[J].中医杂志,2017,58(3):244-249.
[40]BISWAS SK,MANTOVANI A.Macrophage plasticity and interaction with lymphocyte subsets:cancer as a paradigm[J].Nat Immunol,2010,11(10):889-896.
[41]ARNOLD L,HENRY A,PORON F,et al.Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis[J].J Exp Med,2007,204(5):1057-1069.
[42]ODEGAARD JI,CHAWLA A.Alternative macrophage activation and metabolism[J].Annu Rev Pathol,2011,6:275-297.doi:10.1146/annurev-pathol-011110-130138.
[43]SIERRA JR,CORSO S,CAIONE L,et al.Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages[J].J Exp Med,2008,205(7):1673-1685.
[44]NARDIN A,ABASTADO JP.Macrophages and cancer[J].Front Biosci,2008,13:3494-3505.
[45]DE LAS CE M,CORBI AL.Serotonin modulation of macrophage polarization:inflammation and beyond[J].Adv Exp Med Biol,2014,824:89-115.doi:10.1007/978-3-319-07320-0_9.
[46]庄灿皇.基于近二十年文献中医药治疗肝纤维化的方药规律研究[D].广州:广州中医药大学,2016:15-20.
[2]FRIEDMAN SL.Mechanisms of hepatic fibrogenesis[J].Gastroenterology,2008,134(6):1655-1669.
[3]ROCKEY DC.Translating an understanding of the pathogenesis of hepatic fibrosis to novel therapies[J].Clin Gastroenterol Hepatol,2013,11(3):224-231.
[4]THOMAS JA,POPE C,WOJTACHA D,et al.Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis,regeneration,and function[J].Hepatology,2011,53(6):2003-2015.
[5]HAIDERI SS,MCKINNON AC,TAYLOR AH,et al.Injection of embryonic stem cell derived macrophages ameliorates fibrosis in a murine model of liver injury[J].NPJRegen Med,2017,2:14.doi:10.1038/s41536-017-0017-0.
[6]VAN DEN BOSSCHE J,NEELE AE,HOEKSEMA MA,et al.Macrophage polarization:the epigenetic point of view[J].Curr Opin Lipidol,2014,25(5):367-373.
[7]LIU YC,ZOU XB,CHAI YF,et al.Macrophage polarization in inflammatory diseases[J].Int J Biol Sci,2014,10(5):520-529.
[8]孙广仁,郑洪新.中医基础理论[M].北京:中国中医药出版社,2012:28-29.
[9]MURRAY PJ,WYNN TA.Protective and pathogenic functions of macrophage subsets[J].Nat Rev Immunol,2011,11(11):723-737.
[10]MANTOVANI A,SICA A,SOZZANI S,et al.The chemokine system in diverse forms of macrophage activation and polarization[J].Trends Immunol,2004,25(12):677-686.
[11]MARTINEZ FO,SICA A,MANTOVANI A,et al.Macrophage activation and polarization[J].Front Biosci,2007,13:453-461.doi:10.1016/B978-0-12-374279-7.03002-2.
[12]TACKE F,ZIMMERMANN HW.Macrophage heterogeneity in liver injury and fibrosis[J].J Hepatol,2014,60(5):1090-1096.
[13]SICA A,INVERNIZZI P,MANTOVANI A.Macrophage plasticity and polarization in liver homeostasis and pathology[J].Hepatology,2014,59(5):2034-2042.
[14]SACHS BD,BAILLIE GS,MCCALL JR,et al.p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/c AMP/PKApathway[J].J Cell Biol,2007,177(6):1119-1132.
[15]KENDALL TJ,HENNEDIGE S,AUCOTT RL,et al.p75 neurotrophin receptor signaling regulates hepatic myofibroblast proliferation and apoptosis in recovery from rodent liver fibrosis[J].Hepatology,2009,49(3):901-910.
[16]ELPEK GO.Cellular and molecular mechanisms in the pathogenesis of liver fibrosis:an update[J].World JGastroenterol,2014,20(23):7260-7276.
[17]WYNN TA.Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases[J].J Clin Invest,2007,117(3):524-529.
[18]HERNANDEZ-GEA V,FRIEDMAN SL.Pathogenesis of liver fibrosis[J].Annu Rev Pathol,2011,6:425-456.doi:10.1146/annurev-pathol-011110-130246.
[19]ELLIS EL,MANN DA.Clinical evidence for the regression of liver fibrosis[J].J Hepatol,2012,56(5):1171-1180.
[20]MCGUIRE RF,BISSELL DM,BOYLES J,et al.Role of extracellular matrix in regulating fenestrations of sinusoidal endothelial cells isolated from normal rat liver[J].Hepatology,1992,15(6):989-997.
[21]SCHUPPAN D,RUEHL M,SOMASUNDARAM R,et al.Matrix as a modulator of hepatic fibrogenesis[J].Semin Liver Dis,2001,21(3):351-372.
[22]LEE JS,SEMELA D,IREDALE J,et al.Sinusoidal remodeling and angiogenesis:a new function for the liverspecific pericyte?[J].Hepatology,2007,45(3):817-825.
[23]ROSMORDUC O,HOUSSET C.Hypoxia:a link between fibrogenesis,angiogenesis,and carcinogenesis in liver disease[J].Semin Liver Dis,2010,30(3):258-270.
[24]JOHNSON A,DIPIETRO LA.Apoptosis and angiogenesis:an evolving mechanism for fibrosis[J].FASEB J,2013,27(10):3893-3901.
[25]WIGHT TN,POTTER-PERIGO S.The extracellular matrix:an active or passive player in fibrosis?[J].Am JPhysiol Gastrointest Liver Physiol,2011,301(6):G950-G955.
[26]GOERDT S,POLITZ O,SCHLEDZEWSKI K,et al.Alternative versus classical activation of macrophages[J].Pathobiology,1999,67(5/6):222-226.
[27]PRADERE JP,KLUWE J,DE MINICIS S,et al.Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in mice[J].Hepatology,2013,58(4):1461-1473.
[28]BENOIT M,DESNUES B,MEGE JL.Macrophage polarization in bacterial infections[J].J Immunol,2008,181(6):3733-3739.
[29]NOEL W,RAES G,HASSANZADEH GG,et al.Alternatively activated macrophages during parasite infections[J].Trends Parasitol,2004,20(3):126-133.
[30]ABRAMSON SL,GALLIN JI.IL-4 inhibits superoxide production by human mononuclear phagocytes[J].JImmunol,1990,144(2):625-630.
[31]MROWIETZ U,SEIFERT O.Keloid scarring:new treatments ahead[J].Actas Dermosifiliogr,2009,100 Suppl2:75-83.
[32]HUNG K,LEE T,CHOU W,et al.Interleukin-10 gene therapy reverses thioacetamide-induced liver fibrosis in mice[J].Biochem Biophy Res Commun,2005,336(1):324-331.
[33]PESCE JT,RAMALINGAM TR,MENTINK-KANE MM,et al.Arginase-1-expressing macrophages suppress Th2cytokine-driven inflammation and fibrosis[J].PLo SPathog,2009,5(4):e1000371.
[34]BAI L,FU L,LI L,et al.Cellular Mechanisms of Hepatoprotection Mediated by M2-Like Macrophages[J].Med Sci Monit,2018,24:2675-2682.doi:10.12659/MSM.907222.
[35]PELLICORO A,RAMACHANDRAN P,IREDALE JP,et al.Liver fibrosis and repair:immune regulation of wound healing in a solid organ[J].Nat Rev Immunol,2014,14(3):181-194.
[36]DULTZ G,GERBER L,FARNIK H,et al.Soluble CD163 is an indicator of liver inflammation and fibrosis in patients chronically infected with the hepatitis B virus[J].J Viral Hepat,2015,22(4):427-432.
[37]宛硕,黄艳,陈庭金,等.巨噬细胞极化的研究进展[J].中国病原生物学杂志,2015,10(11):1051-1054.
[38]高晓宇,张哲,王洋,等.基于脾虚生痰理论探讨巨噬细胞自噬与动脉粥样硬化的关系[J].中医杂志,2017,58(22):1902-1905.
[39]蒙玉娇,何秀娟,林燕,等.回阳生肌膏拆方对慢性皮肤溃疡模型小鼠疮面愈合及疮面巨噬细胞表型转化的影响[J].中医杂志,2017,58(3):244-249.
[40]BISWAS SK,MANTOVANI A.Macrophage plasticity and interaction with lymphocyte subsets:cancer as a paradigm[J].Nat Immunol,2010,11(10):889-896.
[41]ARNOLD L,HENRY A,PORON F,et al.Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis[J].J Exp Med,2007,204(5):1057-1069.
[42]ODEGAARD JI,CHAWLA A.Alternative macrophage activation and metabolism[J].Annu Rev Pathol,2011,6:275-297.doi:10.1146/annurev-pathol-011110-130138.
[43]SIERRA JR,CORSO S,CAIONE L,et al.Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages[J].J Exp Med,2008,205(7):1673-1685.
[44]NARDIN A,ABASTADO JP.Macrophages and cancer[J].Front Biosci,2008,13:3494-3505.
[45]DE LAS CE M,CORBI AL.Serotonin modulation of macrophage polarization:inflammation and beyond[J].Adv Exp Med Biol,2014,824:89-115.doi:10.1007/978-3-319-07320-0_9.
[46]庄灿皇.基于近二十年文献中医药治疗肝纤维化的方药规律研究[D].广州:广州中医药大学,2016:15-20.