[摘 要]中药药效物质基础是指中药中含有的能够表达药物临床疗效的化学成分总称.而中医临床使用的是方剂,中药饮片是原料,方剂才是药物.同一中药在不同配伍环境下在体内表达不同的体内直接作用物质,从而实现药效的配伍取向.所以中药药效物质基础研究应该从方剂入手,而评价方剂的临床药效是发现药效物质基础的前提.在临床上,方剂对应的是证候或病,中医证候/病的客观正确诊断,阐释证候/病的生物学本质,发现证候/病的生物标记物,建立临床疗效的生物评价体系是评价方剂临床疗效进而发现中药药效物质基础的基本前提.基于中药复方给药形式的特殊性及方证对应疗效的专属性,笔者的团队以证候为起点,从方剂入手,建立了系统的关联“证候诊断-方剂效应评价-体内直接作用物质分析”的方法学――中医方证代谢组学(Chinmedomics),将中药血清药物化学和代谢组学有机结合,在解决证候生物标记物的基础上,建立方剂药效生物评价体系,发现并确定中药药效物质基础,进而解决与药效物质基础相关的中药有效性及安全性等质量问题,以及基于临床有效性的中药创新药物发现问题.
[关 键 词]中医方证代谢组学,中药血清药物化学,代谢组学,体内药效物质基础,方法学
[收稿日期]2014-12-02
[基金项目]国家自然科学基金重点项目(81470093)
[通信作者]王喜军,教授,Tel:(0451)82110818,E-mail:xijunw@sina.
Methodologyforsystematicanalysisofinvivoefficacymaterialbaseof
traditionalChinesemedicine--Chinmedomics
WANGXi-jun
(HeilongjiangUniversityofChineseMedicine,Harbin150040,China)
[Abstract]TheefficacymaterialbaseoftraditionalChinesemedicines(TCMs)isthoseconstituentsabsorbedinbloodandshowtheefficacyofTCMsafteroraladministrationofaTCMformula.InTCM,formulaconsistedofmorethanoneherbaldrugistheclinicalmedicationformwhichcorrespondingtoTCMsyndrome.TheefficacymaterialbaseofTCMshadtobefoundintheconditionofpatibilityandefficacyofTCMformula.ThereforewetakethebiologicalcharactersofTCMsyndromeasaresearchstartingpoint,takingformulaasobject,throughtheintegrationofserumpharmacochemistryofTCMmethodsandmetabolomicstechnologies,establishasystemresearchmethodologyoftheefficacymaterialbasisinvivo--Chinmedomics.Theuseofmetabolomicstechnologyisusedtofullyunderstandnaturebiologyonsyndromesordisease,identifybiomarkerordiseasetobridgingdiseaseanimalmodel,establishingthebiologicalevaluationsystemoftraditionalChinesemedicine.Onthebasisofthevalidityofthepremise,theuseofserumpharmacochemistryofTCMtoanalysisinvivodirectlysubstanceafteroralprescriptionanddynamiclaw,binedwithchangeslawoftheendogenousdiseasebiomarkers(pharmacodynamicmarkersofTCM),ThoughestablishingtwovariablecorrelationanalysiethodbetweenChinesechemicalpositionsinserumexogenousandendogenousbiomarkers,toextractTCMpositionshighlycorrelatedwiththeendogenouarkeraspotentialbasiortraditionalChinesemedicines,andtobiologicalvalidationtodeterminetheefficacymaterialbasisofTCM.
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[责任编辑张宁宁]