血瘀证和活血化瘀治疗临床研究ppt课件.ppt

1,血瘀证和活血化瘀治疗临床研究ClinicalResearchonBlood-stasisSyndrome(BSS)andActivating-blood-circulation(ABC)Treatment,.,2,血瘀证,BSS,XueYuZhengOketsuSyndromeEohyul(血流不畅，血液淤滞的一种证候）,具有中国传统医学特色的一种综合征诊断国际传统医学界认同涉及病种多,临床实践指导意义大,3,多种病可归入血瘀证范畴(1)Manykindsofmoderndiseasesand/ortheirclinicalmanifestationscouldbediagnosedwithinBSScategory,心血管系统：冠心病心绞痛，急性心肌梗死，风湿性心脏病，心力衰竭，各类脉管炎等神经精神系统：脑中风，脑外伤，慢性头痛，震颤麻痹，周围神经疾病，精神分裂症血液系统疾病：真性红细胞增多症，紫癜，再障，弥漫性血管内凝血，高粘血症等消化系统：溃疡病，胃炎，消化道出血，慢性肝炎，肝纤维化呼吸系统：慢性阻塞性肺疾病，高原反应等泌尿系统：急慢性肾炎，血尿等免疫系统：硬皮病，红斑狼疮，类风湿性关节炎，荨麻疹，血管神经性水肿等,4,多种病可归入血瘀证范畴(2)Manykindsofmoderndiseasesand/ortheirclinicalmanifestationscouldbediagnosedwithinBSScategory,代谢系统：高脂血症，糖尿病神经血管并发症等结缔组织系统：灼伤及外伤性皮肤瘢痕，角膜瘢痕等妇产科：功能性子宫出血，痛经，子宫内膜异位症，宫外孕，盆腔炎，子宫肌瘤等儿科：新生儿硬肿症，肝炎及紫癜等皮肤科：红斑结节类病，色素沉着性病，酒糟鼻眼科：视网膜血管阻塞病，眼部免疫病及退行性病口腔及耳鼻喉科：三叉神经痛，突发性聋等骨科：骨折等外科：部分急腹症等肿瘤科：血管瘤，肝癌等器官移植：排异反应等,5,中国传统医学特色诊断：血瘀证ChineseMedicineFeaturesDiagnosis-BSS,久病多瘀（慢瘀）温热病重症必瘀（热瘀）创伤外症多瘀（伤瘀）急症多瘀（急瘀）老年多瘀（老瘀）寒凝致瘀（寒瘀）紫舌无症状（潜瘀,前瘀）,6,主要依据,生物流变学特点（血管流变学及血液流变学所见）宏观生物流变学（血液粘度，血浆粘度，血管壁应力，微血管应力）微观生物流变学（红细胞聚集性及变形能力，红细胞血小板表面电荷水平；血细胞性状、粘附性及变形性；血浆蛋白含量，凝血因子，细胞膜功能，神经介质，免疫因子，血栓素等水平）,真性红细胞增多症、肺心病、心衰、高原反应、脑梗塞、心肌梗塞、周围血管阻塞、休克、高脂血症、高血压、原发性骨髓瘤、多数肿瘤、烧伤、创伤、脱水、增龄改变、DIC、甲亢、经期妇女、妊娠、红斑狼疮、视网膜静脉阻塞、ARDS、部分感染等,失血、贫血、晚期肿瘤、尿毒症、肝硬变腹水、酒精中毒、部分白血病、部分月经病、红细胞膜损伤等,血瘀证的现代分类BSSmodernclassification,7,Bloodandvesselsstasis血脉凝泣Evilblood恶血Retainedblood留血Vascularobstruction脉不通Injuredbloodstasis损伤瘀血Blood-stasisduetoaccumulatedcold寒凝瘀血Blood-stasisduetoanger大怒瘀血,血瘀证的经典概念(1)ClassicalConceptsofBSS,Quotedfrom“InnerClassicoftheYellowEmperor”(WestHanDynasty,100B.C.)（选引自黄帝内经）,8,血瘀证的经典概念(2)ClassicalConceptsofBSS,Blood-stasisduetochronicdisorders病久入深瘀血Blood-stasiswithsuddenpainoforgans瘀血“五藏卒痛”Blood-stasiswitharthralgia瘀血痹证Syncopeduetoblood-stasis瘀血厥证Carbuncleduetoblood-stasis瘀血成痈Blood-stasiswithbloodexhaustion瘀血血枯,Quotedfrom“InnerClassicoftheYellowEmperor”(WestHanDynasty,100B.C.)（选引自黄帝内经）,9,“Stagnationbloodaccumulatedincertainchannelororgan”,ExtractedfromDr.ZhangZhong-jings“GoldenChamber”and“OnFebrile”(EastHanDynasty,142220A.D.)（选引自张仲景伤寒论、金匮要略)）,“瘀血病脉证治”专论,10,“Manychronicdiseasescouldhaveblood-collateraldisturbances”(“久病入络”),QuotedfromDr.YeTian-shis“ClinicalGuidancewithCaseStudies”(QingDynasty,16671746A.D.)（选引自叶天士临证指南医案）,慢性疾病血瘀证,11,“Althoughthereweremanycausesofdiseases,theyfellmainlyintotwogroups:disturbancesQiandXue(blood).TherewerestrongandweakQi,andthereweretheanemicandcongealedblood(stasis)”.Dr.WanglistedfiftymorediseasesduetoBSSinhisbook.（“治病之要决在于明气血，气有虚实，血有亏瘀”）,AdoptedfromDr.WangChing-rens“CorrectionsinChineseMedicine”(QingDynasty,17681831A.D.)（引自王清任医林改错）,临床重视血瘀证的治疗,12,十纲辨证(Diferentiationwithtenprinciplesyndromes),+气血辨证气虚、气陷、气滞、气逆血虚、血瘀、血热气滞血瘀、气虚血瘀、气血两虚气虚失血、气随血脱、痰瘀互结,阴阳、寒热、表里、虚实,PrincipleSyndromesfromeighttoten,13,血瘀证基本诊断条件(1)FundamentalconditionsforBSSdiagnosis,Purpleofthetongue,orpurpledotsorscarsonthetongue舌质紫黯或有瘀斑、瘀点Hesitantpulse,orslowandunevenpulse,andintermittentpulse,orlackofpulse涩脉、间歇脉、或无脉Constantpricklypainorcolicpainwithresistanceofpressing痛有定处，不喜按Pathologicalmassincludingorganicenlargement,newlymass,inflammatorymass,histologicalhyperplasiaordegeneration瘀积肿块,14,血瘀证基本诊断条件(2)FundamentalconditionsforBSSdiagnosis,Abnormalbloodvesselsincludingvaricosityofundertongueorotherparts,capillarydilation,spasm,cyanosisoflipsorextremeties,obstruction舌下或他处瘀阻，唇或四肢青紫，梗阻Bleedinganditsconsequenceasblood-stool,subcutaneouspurplescars出血及其后遗证如黑便及皮下瘀斑,15,血瘀证其他诊断条件Otherconditions(manifestationduetoblood-stasis)forBSSdiagnosis,Roughskin,skinhypertrophyoralligatorskin-crumps肌肤甲错Menstruationdisorder月经失调Numbnessofextremetiesorhemiplegia肢体麻木或偏瘫Maniawithemotionalexcitementoramnesia(forgetfulness)情志记忆失常Periodicalmentaldysfunction周期性精神失常Ascites腹水,16,血瘀证实验室所见LaboratoryfindingsforBSSdiagnosis,Microcirculationdisturbance微循环失调Abnormalhemorheology血流变学异常Hemodynamicchanges血流动力学异常Platelethyperaggregation血小板聚集性增高Cerebro-vascularthrombosisorembolism脑血管梗塞Ultrastructuralblood-stasisbyEcho,angiographyorCT/MRIexamination超声、血管造影或CT/MRI所见超微结构血瘀征象,17,临床研究用定量血瘀证诊断标准记分方法TheBSSscoresforclinicaldiagnosis,注:判断标准以19分以下为非血瘀证;2049分为轻度血瘀证;50分以上为重度血瘀证,18,三类活血化瘀药物ThreeKindsofABCHerbs,1.和血类药物Blood-harmonizingherbsDanggui(Angelicasinensis)当归Danpi(PaeoniasuffruticosaAndr.)丹皮Danshen(SalviamiltiorrhizaBge.)丹参Shengdihuang(glutinosa)生地黄Chishao(paeonia)赤芍Jixueteng(spatholobussuberectus)鸡血藤,19,Chuanxiong(Ligusticum)川芎Puhuang(Typhaangustifolia)蒲黄Honghua(Carthamustinctorius)红花Liujinu(ArtemisiaanomalaS.Moore)刘寄奴Wulingzhi(Trogopterusxanthipes)五灵脂Yujin(CurcumaaromaticaSalisb.)郁金Sanqi(Panaxnotoginseng)三七Chuanshanjia(Manispentadactyla)穿山甲Jianghuang(CurcumalongaL.)姜黄Yimucao(LeonurusheterophyllusSweet)益母草Zelan(LycopuslucidusTurcz.)泽兰,2.活血类药物Blood-activatingherbs,三类活血化瘀药物ThreeKindsofABCHerbs,20,2.活血类药物Blood-activatingherbsSumu(CaesalpiniasappanL.)苏木Haifengteng(PiperfutokadsuraSieb.)海风藤Yizhihao(ParispolyphyllaSmith)一枝蒿Niuxi(AchyranthesbidentataBlume)牛膝Mabiancao(VerbenaofficinalisL.)马鞭草Yanhusuo(CorydalisturtschaninoviiBess.f.)延胡索Guijianyu(BidensbipinnataL.)鬼见羽Ziwei(Campsisgrandiflora)紫葳Wine酒,三类活血化瘀药物ThreeKindsofABCHerbs,21,3.破血类药物Blood-stasis-removingherbsDahuang(RheumpalmatumL.)大黄Shuizhi(Whitmaniapigra)水蛭Mengchong(TabanusbivittatusMats.)虻虫Sanleng(SparganiumstoloniferumBuch.-Ham.)三棱Erzhu(Curcumazedoaria)莪术Ruxiang(BoswelliacarteriiBirdw.)乳香Moyao(CommiphoramyrrhaEngl.)没药Xuejie(DaemonoropsdracoBl.)血竭Taoren(Prunuspersica)桃仁,三类活血化瘀药物ThreeKindsofABCHerbs,22,神农本草经确载活血化瘀药分析,41/365种丹参、牡丹皮、牛膝、芍药、桃仁、虻虫、蛰虫、川芎、鳖甲、蛴螬、乌贼骨等大黄、柴胡之推陈致新作用,23,活血化瘀药,即美国医药学界习称之ABC药ActivatingBloodCirculationHerbsPromotingBloodCirculationtoRemoveBlood-stasis,24,活血化瘀兼治痰瘀药物举隅ExamplesofrelievingBSSandphlegmaccumulationsherbs,25,34种活血化瘀药的比较研究,观察指标(26项)：血液粘滞血小板功能红细胞变形性血栓形成试验冠脉流量心肌收缩力心肌细胞耗氧量其他,26,血瘀证治疗原则和方剂(1)TherapeuticprinciplesandformulasforBSS,TonifyingQiandactivatingbloodcirculation益气活血（BuYangHuanWuTangFormula补阳还五汤）ModulatingQiandactivatingbloodcirculation理气活血（XueFuZhuYuTangFormula血府逐瘀汤，DanShenYinFormula丹参饮）WarmingChannelandactivatingbloodcirculation温经活血（WenJingTangFormula温经汤）Antitoxicandpromotingbloodcirculation解毒活血（XianFangHuoMingYinFormula仙方活命饮）Coolingbloodandremovingblood-stasis凉血祛瘀（XiJiaoDiHuangTangFormula犀角地黄汤）,27,Nourishingbloodandpromotingbloodcirculation养血活血（TaoHongSiWuTangFormula桃红四物汤）Purgativeswithremovingblood-stasis通腑祛瘀（TaoHeChengQiTangFormula桃核承气汤）TonifyingYangandpromotingbloodcirculation补阳活血（ShengHuaTangFormula生化汤）EliminatingWindandremovingblood-stasis祛风化瘀（ShenTongZhuYuTangFormula身痛逐瘀汤）Openingorificeandpromotingbloodcirculation开窍活血（TongQiaoHuoXueTangFormula通窍活血汤）Dispersinglumpsandremovingblood-stasis散结化瘀（GuiZhiFuLingWanFormula桂枝茯苓丸）,血瘀证治疗原则和方剂(2)TherapeuticprinciplesandformulasforBSS,28,日本常用活血化瘀方剂及其组成,注：（1）伤：指伤寒论，金：指金匱要略;（2）重者，用偏寒性及虫类药,29,张仲景活血化瘀古方新用,当归芍药散（痴呆，记忆功能障碍）大黄牡丹皮汤（阑尾炎）温经汤（闭经、带证）鳖甲煎丸（肝脾肿大）大黄蛰虫丸（风心病）桃仁承气汤（精神神经疾患）下瘀血汤（产后腹痛）抵当汤（月经不利）红蓝花酒（妇女病、心痛）王不留行散（外伤性出血）,30,黄帝内经的活血化瘀方剂,四乌贼骨一芦茹丸组成:茜草,乌贼骨,鲍鱼,雀卵功效:活血化瘀,温经补肾,31,医学衷中参西录(张锡纯)治白带恶臭医方,理带汤乌贼骨、茜草、生龙牡、山药,32,抗心梗合剂(AMIMixture),组成：黄芪30g、党参15g、黄精15g、丹参30g、赤芍15g、郁金15g功效：益气活血PlantaMedica,1983;48(1):63-64,33,愈梗通瘀汤(自拟,1990),组成：生晒参1015g，生黄芪15g，紫丹参15g，全当归10g，延胡索10g，川芎10g，广藿香1218g，佩兰1015g，陈皮10g，半夏10g，生大黄610g功效：益气活血，祛瘀抗栓，利湿化浊适应症：用于心肌梗死急性期及恢复期患者，能够促进梗塞组织愈合，保护心功能，改善生存质量，延长寿命处理好通与补的关系,34,人参三七元胡粉(郭士魁经验方,1985)人参三七琥珀粉(岳美中经验方,1964),人参三七元胡粉（1.5:1.5:3）:益气活血，理气定痛人参三七琥珀粉（1.5:1.5:0.5）:益气，活血，安神,35,活血化瘀八个古方主要药效学作用比较,36,八个经典古方的比较研究,37,活血化瘀方临床治疗应用ClinicaltrialofABCformulasforcertaindiseases,抗心绞痛和抗血小板治疗Treatmentofanti-anginapectorisandanti-platelet预防冠心病PTCA/支架治疗后再狭窄PreventionofrestenosisafterPTCA/stentinginCHD血府逐瘀汤及其有效部位的应用BytheapplicationofXueFuZhuYuTangFormula,38,冠心号复方组成,川芎Ligusticumwallichii赤芍Paeoniaobovata丹参Salviamiltiorrhiza红花Carthamustinctorius降香Dalbergiaodorifera,39,冠心号类活血药的临床应用,40,冠心病不同治法的疗效比较,编者按：本文是一篇水平较高的工作总结，其突出的优点是研究的设计和方法使临床资料具有较好的对比性，因而，它的结论就具有较强的说服力。,中华心血管病杂志1982年第10卷第2期临床论著精制冠心片双盲法治疗冠心病心绞痛112例疗效分析,42,精制冠心片,精制冠心颗粒,43,44,扩大活血化瘀治疗范围达54种疾病，充分发挥中医药优势，特别是心脑血管病疗效明显提高个体化、合理应用、方证相应,是取得疗效的前提,活血化瘀治法的推广应用-活血化瘀现象,45,川芎嗪对缺血性中风的效果TheefficacyofLigustrazineforIschemicStroke,Tetramethylpyrazine,46,川芎嗪毒性与代谢ToxicityandmetabolismofLigustrazine,LD50:239mg/kg(rat)half-life:29.26min(blood)(rabbit)PassingthroughBBB(Brainstem:cerebrum=4:1),47,川芎嗪抗血栓素(thromboxane)生成作用,InhibitoryeffectofABC-herbsonTXB2production,48,抗血小板中药示例Anexampleofherbalantiplateletdrug,Ligustrazinewasalsodemonstratedtolowerplateletintracellularcalciumandinhibitsecretionofplatelet-granules.Duetoexactantiplateleteffect,LigustrazinehasbeenacommondrugintreatingcerebralischemiaandischemicstrokeinurbanandruralareainChinaatpresent.,49,川芎嗪静脉应用对缺血性中风临床疗效TheclinicalefficacyonischemicstrokebyIVusewithLigustrazine,Comparedwithpapaverineclinicalcurativerate：43与40remarkableeffectiverate：23与22effectiverate：23与10noneeffectiverate：11与22totaleffectiverate：88.6与78.0%(administrations：ivgtt,80mg/d10),50,中药抗血小板作用AntiplateleteffectofChineseMedicine,ChiShao,RadixPaeoniaerubra赤芍DanShen,RadixSalviaeMiltiorrhizae丹参ChuanXiong,RhizomaLigusticumWallichii川芎PuHuang,PollenTyphae蒲黄YiMuCao,HerbaLeonuri益母草WangBuLiuXing,SemenVaccariae王不留行HongHua,FlosCarthami红花,51,其他抗血小板中药有效成分Othereffectivecomponentsisolatedfromherbalmedicinesforantiplatelet,Ferulioacid(阿魏酸)TanshinPhenolicAcidsA(丹参素)PropylGallate(赤芍801,没食子酸丙酯)Berberine(小檗碱)Saponinofnotoginseng(三七皂甙)芍药酚52021(银杏内酯)Tetrandrine(粉防己碱)Quercetin(槲皮素)Kadsurenone(海风藤酮)(新灯盏花素)甲基莲心碱()Rhynchophylline(钩藤碱)Ginsenosides(人参总皂甙)Gypenosides(绞股蓝总皂甙)黄山药总皂甙蒺藜总皂甙,52,阿魏酸和川芎嗪(FATM)组合对ADP诱导的血小板体内凝集的抑制作用(n=7),与NS组比较：a:P0.01;与TMPz组比较：b:P50%)；行PTCA及冠脉内支架植入术成功的患者；或AMI患者行急诊介入治疗成功的患者中医辨证分型不限,75,ExclusionCriteria,RestenosislesionorgraftvessellesionChroniccompletelyobstructivelesion(3mons)；Severeleftmainarterylesion;Severeheartfailure(EF3个月)；严重左主干病变；严重心功能不全(EF35%)；未控制的级高血压患者；严重瓣膜性心脏病;合并严重肝、肾、造血系统、神经系统等原发性疾病及精神病、恶性肿瘤患者患者拒绝签署知情同意书，或估计依从性较差；参加其他临床试验的患者；妊娠期或哺乳期妇女。,76,ClinicalandAngiographicEndPoints,PrimaryendpointAngiographicrestenosisClinicalendpointsDeathNonfataltargetlesionmyocardialinfarctionCoronaryarterybypassgraftsurgeryRepeattarget-vesselangioplasty,临床及冠造终点,主要研究终点冠脉造影所示再狭窄临床研究终点死亡病变血管出现非致命性心肌梗死重复血管成形术冠状动脉搭桥术,77,Follow-upofpatients,Theclinicalfollow-upvisitwasscheduled1,3and6monthsafterPCIforclinicalandlaboratoryassessment.Patientcompliancewasassessedbyreturnedemptybottlesofthetrialdrug.RepeatCAGwasrequiredat6monthsafterPCItoassessangiographicrestenosis.,患者随访,术后1个月、3个月及6个月门诊复查，通过患者服完药的药瓶监测其服药的依从性。术后6个月行冠脉造影复查，以评估冠脉造影再狭窄的情况。临床终点事件随访至术后1年。,78,研究概况StudyOutline,335casesenrolled335例入选,Controlgroup对照组169cases,Treatmentgroup治疗组166cases,308casescompletedwith145repeatangiography308例完成试验，145例重复冠脉造影,Randomize随机,3caseslost脱落,12casesexclude剔除,3caseslost脱落,9casesexclude剔除,154cases,154cases,(47.08%),79,基线临床资料比较BaselineClinicalCharacteristics,治疗组,对照组,P值,80,基线冠脉造影资料比较BaselineAngiographicCharacteristics,81,Comparisonofclinicalend-pointevent两组临床终点事件的比较,Note:Therewassignificantdifferencebetweenthetwogroups(p0.05).,两组临床结果比较ClinicalOutcome,82,TreatmentPlacebo,83,Note:Comparedwithcontrolgroup，*P0.05,两组冠脉造影结果比较AngiographicOutcome,注:与对照组比较，*P0.05,84,Note:Comparedwithcontrolgroup，*P0.05,两组冠脉造影结果比较AngiographicOutcome,注:与对照组比较，*P0.05,85,PlaceboTreatment,Figure.Cumulativedistributionplotofminimumlume