Exosome在针刺信息传导中的网络调节作用探讨
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摘要
针灸作用有别于西药"点-点""点-系统"的靶向作用,网络调节是针刺作用的最基本模式。外泌体(exo-some)是机体神经、内分泌、免疫系统细胞间通讯的重要载体,前期研究发现针刺可调节外泌体释放且与针效之间可能存在一定关系。以exosome为切入点,以针刺足三里治疗佐剂性关节炎大鼠为研究平台,利用蛋白组学技术检测针刺血清exosome内含全蛋白成分,构建针刺蛋白网络图谱。利用代谢组学技术检测针刺大鼠血清exosome内含代谢物,构建针刺代谢网络图谱。整合蛋白组学及代谢组学实验数据,结合当前针刺机制研究文献证据,利用分子生物信息学方法绘制针刺网络调节图谱,应用复杂网络等数据挖掘技术分析网络关键响应子,通过缺失/捕获技术调控exosome或关键响应子的表达,观察对针刺疗效的影响,可初步揭示针刺网络调节的生物学基础,研究提高针刺疗效的新方法,探索符合中医整体观念的研究新模式。
Acupuncture and moxibustion are different from the"point to point"and"pointsystem"of Western medicine. Exosome is an important way of communication between the nervous system,endocrine system and immune system,and it is found that acupuncture can regulate the release of the exocrine. This project takes exosome as the starting point,with acupuncture treatment in adjuvant arthritis rats as the research platform,using proteomics technique for the detection of serum exosome protein containing all components of acupuncture,acupuncture of protein network construction. We detected serum exosome metabolites in rats serum by metabonomics technique,and construction of acupuncture metabolic network. The data integration of proteomics and metabolomics,combined with the current research on mechanism of acupuncture literature evidence,using molecular biological information network regulation method of drawing acupuncture,application of complex network data mining technology analysis of network keyresponse,through the regulation of exosome expression deletion/capture or subcritical response,we observed the influence on the therapeutic effect of acupuncture and revealed its important role in the process of acupuncture information conduction and improving the curative effect of acupuncture,and explored new ways of modern scientific research. It has the characteristics of Chinese medicine acupuncture and moxibustion.
Acupuncture and moxibustion are different from the"point to point"and"pointsystem"of Western medicine. Exosome is an important way of communication between the nervous system,endocrine system and immune system,and it is found that acupuncture can regulate the release of the exocrine. This project takes exosome as the starting point,with acupuncture treatment in adjuvant arthritis rats as the research platform,using proteomics technique for the detection of serum exosome protein containing all components of acupuncture,acupuncture of protein network construction. We detected serum exosome metabolites in rats serum by metabonomics technique,and construction of acupuncture metabolic network. The data integration of proteomics and metabolomics,combined with the current research on mechanism of acupuncture literature evidence,using molecular biological information network regulation method of drawing acupuncture,application of complex network data mining technology analysis of network keyresponse,through the regulation of exosome expression deletion/capture or subcritical response,we observed the influence on the therapeutic effect of acupuncture and revealed its important role in the process of acupuncture information conduction and improving the curative effect of acupuncture,and explored new ways of modern scientific research. It has the characteristics of Chinese medicine acupuncture and moxibustion.
引文
[1]WHO.Acupuncture:review and analysis of reports on controlled clinical trials.http://apps.who.int/iris/bitstream/10665/42414/1/9241545437.pdf
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[14]Yanqiong Zhang,Ming Bai,Bo Zhang,et al.Uncovering pharmacological mechanisms of Wu-tou decoction acting on rheumatoid arthritis through systems approaches:drug-target prediction,network analysis and experimental validation[J].Scientific Reports,2015,5:9463.
[15]Zhang-Jin zhang,Xiao-Min Wang,Grainne M.Neural Acupuncture Unit:A new comcept for interpreting effects and mechanisms of acupuncture[J].Evidence-Based Complementary and Alternative Medicine,2012:1-23.
[16]Ji-Yeun Park,Jongbae J,Songhee Jeon,et al.From Peripheral to Central:The Role of ERK Signaling Pathwayin Acupuncture Analgesia[J].The Journal of Pain,2014,15(5):535-549.
[17]Tkach M,Théry C.Communication by Extracellular Vesicles:Where We Are and Where We Need to Go[J].Cell,2016,164(6):1226-1232.
[18]Srinivasan S,Vannberg FO,Dixon JB.Lymphatic transport of Exosomes as a rapid route of information dissemination to the lymph node[J].Scientific Reports,2016,6:24436.
[19]Zappulli V,Friis KP,Fitzpatrick Z,et al.Extracellular vesicles and intercellular communication within the nervous system[J].Journal of Clinical Investigation,2016,126(4):1198-1207.
[20]Théry CM,Ostrowski E,Segura.Membrane vesicles as conveyors of immune responses[J].Nature Reviews Immunology,2009,9(8):581-593.
[21]Rossaint J,Kühne K,Skupski J,et al.Directed transport of neutrophil-derived extracellular vesiclesenables platelet-mediated innate immune response[J].Nat Commun,2016,15(7):13464.
[22]潘萍,郭义.肥大细胞是针刺效应信号放大的关键因素之一[J].辽宁中医杂志,2009,36(12):2066-2068.
[23]陈波,李明月,郭义,等.肥大细胞源性外来体参与构建针刺穴位效应启动小网络的探讨[J].针刺研究,2015,40(1):82-85.
[24]Boulanger Chantal M,Loyer Xavier,Rautou Pierre Emmanuel,et al.Extracellular vesicles in cornoary artery disease[J].Nat Rev Cardiol,2017,14:259-272.
[25]刘良.充分利用组学技术研究及发展中医药[J].世界科学技术-中医药现代化,2009,11(2):214-219.
[26]贾伟,蒋健,刘平,等.代谢组学在中医药复杂理论体系研究中的应用[J].中国中药杂志,2006,31(8):621-624.
[2]杜元灏.现代针炙病谱[M].北京:人民卫生出版社,2009.
[3]韩济生.针刺镇痛原理研究[J].针刺研究,1984(3):231-245,236.
[4]Tang Y,Yin HY,Rubini P,et al.Acupuncture-Induced Analgesia:ANeurobiological Basis in Purinergic Signaling[J].Neuroscientist,2016,22(6):563-578.
[5]Sang-Hak Lee,Seok-Hee Chung,Jong-Soo Lee,et al.Effects of acupuncture on the 5-hydroxytryptamine synthesis and tryptophan hydroxylase expression in the dorsal raphe of exercised rats[J].Neurosci Lett,2002,332(1):17-20.
[6]黄猛,谢英元,丁光宏.穴位注射组胺在急性佐剂性关节炎大鼠上引起的镇痛效应[J].针刺研究,2010(2):99-103.
[7]Lee HJ,Lee JH,Lee EO,et al.Substance P and beta-endorphin mediate electro-acupuncture induced analgesia in mouse cancer pain model[J].J Exp Clin Cancer Res,2009,28(34):137.
[8]Takeshige C,Tsuchiya M,Guo SY,et al.Dopaminergic transmission in the hypothalamic arcuate nucleus to produce acupuncture analgesia in correlation with the pituitary gland[J].Brain Res Bull,1991,26(1):113-122.
[9]Langevin HM,Wayne PM,Mac Pherson H,et al.Paradoxes in Acupuncture Research:Strategies for Moving Forward[J].EvidenceBased Complementary and Alternative Medicine,2011,2011:180805.
[10]郭义.实验针灸学[M].北京:中国中医药出版社,2008:136-142.
[11]陈静子,郭义.基于针刺镇痛的针刺作用特点探讨[J].吉林中医药,2010,30(4):326-327.
[12]沈自尹,系统生物学和信息医学在中西医结合中的应用[J].中西医结合学报,2006,4(2):111-113.
[13]Chen Bo,Li Ming-yue,Ding Sha-sha,et al.Research progress on regulations on nerve-endocrine-immune network by acupuncture[J].World Journal of Acupuncture-Moxibustion,2014,24(4):49-58.
[14]Yanqiong Zhang,Ming Bai,Bo Zhang,et al.Uncovering pharmacological mechanisms of Wu-tou decoction acting on rheumatoid arthritis through systems approaches:drug-target prediction,network analysis and experimental validation[J].Scientific Reports,2015,5:9463.
[15]Zhang-Jin zhang,Xiao-Min Wang,Grainne M.Neural Acupuncture Unit:A new comcept for interpreting effects and mechanisms of acupuncture[J].Evidence-Based Complementary and Alternative Medicine,2012:1-23.
[16]Ji-Yeun Park,Jongbae J,Songhee Jeon,et al.From Peripheral to Central:The Role of ERK Signaling Pathwayin Acupuncture Analgesia[J].The Journal of Pain,2014,15(5):535-549.
[17]Tkach M,Théry C.Communication by Extracellular Vesicles:Where We Are and Where We Need to Go[J].Cell,2016,164(6):1226-1232.
[18]Srinivasan S,Vannberg FO,Dixon JB.Lymphatic transport of Exosomes as a rapid route of information dissemination to the lymph node[J].Scientific Reports,2016,6:24436.
[19]Zappulli V,Friis KP,Fitzpatrick Z,et al.Extracellular vesicles and intercellular communication within the nervous system[J].Journal of Clinical Investigation,2016,126(4):1198-1207.
[20]Théry CM,Ostrowski E,Segura.Membrane vesicles as conveyors of immune responses[J].Nature Reviews Immunology,2009,9(8):581-593.
[21]Rossaint J,Kühne K,Skupski J,et al.Directed transport of neutrophil-derived extracellular vesiclesenables platelet-mediated innate immune response[J].Nat Commun,2016,15(7):13464.
[22]潘萍,郭义.肥大细胞是针刺效应信号放大的关键因素之一[J].辽宁中医杂志,2009,36(12):2066-2068.
[23]陈波,李明月,郭义,等.肥大细胞源性外来体参与构建针刺穴位效应启动小网络的探讨[J].针刺研究,2015,40(1):82-85.
[24]Boulanger Chantal M,Loyer Xavier,Rautou Pierre Emmanuel,et al.Extracellular vesicles in cornoary artery disease[J].Nat Rev Cardiol,2017,14:259-272.
[25]刘良.充分利用组学技术研究及发展中医药[J].世界科学技术-中医药现代化,2009,11(2):214-219.
[26]贾伟,蒋健,刘平,等.代谢组学在中医药复杂理论体系研究中的应用[J].中国中药杂志,2006,31(8):621-624.