芪藶強心抑制心室重構抗心力衰竭

基礎與臨床研究證據(jù)CADHypCMValvLVDRemodelingLowEFArrhythmiasDeathPumpFailureCHFSymptomsNonCardiacFactorsVentricularRemodelingafterInfarctionandinDiastolicandSystolicHeartFailureJessupetal.NEnglJMed2003;348:2007-2018NeurohormonalmodelofHFMcMurrayJ,PfefferMA.Circulation.2002;105:2099-106.PrimarytargetsoftreatmentinHFJessupM,BrozenaS.NEnglJMed.2003;348:2007-18.氣陽虛乏脈絡瘀阻

尿少水腫絡息成積心室重構、心臟擴大氣虛不能運血陽虛不能化水

“氣分”（神經(jīng)體液調(diào)節(jié)異常）

“水分”（鈉水滁留）

“血分”（血流動力學異常）

益氣溫陽黃芪、附子、人參、桂枝活血通絡丹參、紅花利水消腫

葶藶子、澤瀉、香加皮標本兼治強心、利尿、擴血管緩解心慌氣短、不能平臥、尿少水腫癥狀抑制RASS與交感神經(jīng)減少心室重構

與RASS、交感神經(jīng)系統(tǒng)激活導致心室重構為慢性心衰病機新概念相吻合脈絡學說指導慢性心衰病機、有效組方及作用研究[CellularImmunology2009,260:52-55]ResultsTheeffectofQiliqiangxinontheechocardiographicandhemodynamicparametersintheinfarctedhearts.4g/kg/dayfor4weeksforRatsTheratioofTNF-a/IL-10ininfarctedmyocardialtissuewasreversedbyQiliqiangxin.Conclusion:QiliqiangxinimprovescardiacfunctionofratswithMIthroughregulationthebalancebetweenTNF-aandIL-10.[JCardiovascPharmacol,2012,59(3):268-280]Conclusion:1.QLinhibitsmyocardialin?ammationandcardiomyocytedeathandpromotescardiomyocyteproliferation,leadingtoanamelioratedcardiacremodelingandfunctioninamousemodelofpressureoverload.2.ThepossiblemechanismsmayinvolveinhibitionofangiotensinIItype1receptorandactivationofErbBreceptors.[Americanjournalofhypertension,2012,25,250-260]QL:0.6mg/kg/dayfor4weeksformiceConclusion:1.QLQXimprovesbothsystolicanddiastoliccardiacfunctioninSHRs.2.QLQXdownregulatethecardiacchymasesignalingpathwayandchymase-mediatedangIIproduction.臨床試驗注冊LiX,ZhangJ,HuangJ,MaA,YangJ,LiW,WuZ,YaoC,ZhangY,YaoW,ZhangB,GaoR.AMulticenter,Randomized,Double-Blind,Parallel-Group,Placebo-ControlledStudyoftheEffectsofQiliQiangxinCapsulesinPatientsWithChronicHeartFailure.JAmCollCardiol.2013;62(12):1065-1072.

臨床研究簡介LiX,ZhangJ,HuangJ,MaA,YangJ,LiW,WuZ,YaoC,ZhangY,YaoW,ZhangB,GaoR.AMulticenter,Randomized,Double-Blind,Parallel-Group,Placebo-ControlledStudyoftheEffectsofQiliQiangxinCapsulesinPatientsWithChronicHeartFailure.JAmCollCardiol.2013;62(12):1065-1072.

BNP/NT-proBNP可用于指導

心衰的治療心衰患者治療后BNP/NT-proBNP與基線相比下降達到或超過30%，表明治療奏效如未下降或下降未達標甚至繼續(xù)走高，則表明治療效果不佳，應繼續(xù)增強治療的力度。中國心力衰竭診斷和治療指南2014中華心血管病雜志2014(42):2生物標志物及應用情況推薦類別證據(jù)水平利鈉肽

HF的診斷或排除非臥床，急性IAHF的預后非臥床，急性IA達到GDMT目標非臥床IIaB指導急性失代償性HF治療急性IIbC心肌損傷標志物附加危險分層急性，非臥床IA心肌纖維化標志物附加危險分層非臥床IIbB急性IIbA

2013ACCF/AHAHFGuideline生物

標志物測定建議GDMT,Guideline-DirectedMedicalTherapy;指南導向藥物治療2013ACCF/AHAGuidelinefortheManagementofHeartFailure.E-PublishedonJune5,2013,availableat:[/article.aspx?doi=10.1016/j.jacc.2013.05.019aStudyDesignNT-proBNP的水平變化及下降超過30%的比例

兩組NYHA心功能分級描述和比較LVEF、LVED、6MWD基線與第12周隨訪變化趨勢

明尼蘇達生活質量量表評分變化趨勢心血管復合事件藥物不良事件EDITORIALCOMMENT

—CARDIOTONICMODULATIONINHEARTFAILURE:INSIGHTSFROMTRADITIONALCHINESEMEDICINE

—讓衰竭的心臟更加強勁-中國傳統(tǒng)醫(yī)學給我們的啟示TangWH,HuangY.CardiotonicModulationinHeartFailure:InsightsfromTraditionalChineseMedicine.JAmCollCardiol.2013;62(12):1073-1074.EditorialComment（述評）

-byTangWHW,HuangYItisconceivablethatinthefutureifqiliqiangxinprovestoprovidemorbidityandmortalitybenefitsinrigorousclinicaltrials,itwillfundamentallychallengetheexistingfoundationofscientificinquirybaseduponthepreciseunderstandingofpharmacodynamicsofdrugtherapies.可以想象的是，如果芪藶強心膠囊在未來高質量的臨床研究中提供更多關于其對受試者發(fā)病率、死亡率益處的證據(jù)，那么它將從根本上挑戰(zhàn)現(xiàn)有的關于藥物效應動力學研究的科學觀念。TangWH,HuangY.CardiotonicModulationinHeartFailure:InsightsfromTraditionalChineseMedicine.JAmCollCardiol.2013;62(12):1073-1074.EditorialComment（述評）

-byTangWHW,HuangYYetevenatpresent,thepromisingresultsreportedbyLiandcolleaguesmayhavealreadyopenedtheopportunitytoexplorewiththelatesttechnologieshowsynergisticinteractionsamongactiveTCMingredientscanbenefitthesyndromeofheartfailure.Thisisachallengethatweshouldallwarmlyembrace.現(xiàn)如今，這項富有前景的研究表明李及他的研究同事們已經(jīng)打開了一扇如何利用最新科技研究傳統(tǒng)中藥活性成分在心力衰竭治療中協(xié)同作用的大門。這是一個挑戰(zhàn)，對此我們應該熱烈擁抱。TangWH,HuangY.CardiotonicModulationinHeartFailure:InsightsfromTraditionalChineseMedicine.JAmCollCardiol.2013;62(12):1073-1074.臨床研究證據(jù)級別：由高到低1.隨機對照研究2.前瞻性非隨機對照研究3.回顧性對照研究4.非對照研究或歷史對照研究5.薈萃分析6.病例報道7.評論，教授或其他專家意見

ProfessorJosephS.AlpertEditor-in-Chief,AmericanJournalofMedicine2013.7.19Nanjing中國心力衰竭診斷和治療指南2014（中華心血管病雜志2014(42):2）對芪藶強心臨床試驗結果進行了描述（參考文獻58）dayMISacrifice071421QL21dWorkingmodel:AMIremodelingOurwork:（我們的研究）Project1:TraditionalChineseMedicationQiliqiangxinattenuatescardiacremodelingafteracutemyocardialinfarctioninmiceUnpublisheddataSaline+shamSaline+MIQL+MIQL+ShamResultsUnpublisheddataRemoteRemoteRemoteRemoteBorderInfarctBorderInfarctBorderBorderSaline+MIQL+MISaline+MIQL+MIUnpublisheddataSaline+ShamSaline+MIQL+MIPPARg1PGC1aGAPDHPPARaUnpublisheddata

Reversalexperiments-PPARaPPARgUnpublisheddataMI+QL+PPARgInhibitorMI+QL+PPARgActivatorMI+QLUnpublisheddataPGC1aCb-ActinPPARaQMQM+PPARgInhibitorPPARgDUnpublisheddataMISacrifice071421QL312418dday0123dayMISacrificeQL3dFutureworkAcutephaseRemodelingphaseUnpublisheddataSaline+MIQL+MIUnpublisheddataAcutephase(TTCStaining)NMQMMISacrifice071421QL312418dFigure11ABBPPARaPPARg1PGC-1ab-actinMI+SalineQL+SalineCProject2:ThemataboliceffectsofQLQXonH9C2(invitro)UnpublisheddataBasalOxidativeMetabolismPeakOxidativeMetabolismFigure1:OxidativeMetabolismindicatedbyoxygenconsumptionofH9C2myocytestreatedwithQLatdifferenttimeanddoseAMitochondrialUncouplingMetabolicRelianceBCBasalGlycolysisPeakGlycolysisFigure2:GlycolysisMetabolismindicatedbyoxygenconsumptionofH9C2myocytestreatedwithQLatdifferenttimeanddoseABFigure3:MitochondrialContentmeasuredbymicroscopyandflowcytometryControllQL(48hr)MitotrackerMitotrackerMergeMergeMitochondrialcontentAB待發(fā)表文章:TraditionalChineseMedicationQiliqiangxinattenuatescardiacremodelingafteracutemyocardialinfarctiontargetingPPARR已于3月31號向哈佛大學醫(yī)學院附院心內(nèi)科主任、新英格蘭副主編托尼教授匯報過研究結果受到好評。臨床意義作為預防心肌梗死后心室重構導致心衰的治療策略之一？（B階段）（RAS/BB）QiliqiangxininHeartFailUre：AssESsmentofReductioninMorTality

ProfXinliLiTheFirstAffiliatedHospitalwithNanjingMedicalUniversityonbehalfoftheInvestigatorsStudyDesignTherapeuticregimen: