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1、芪苈强心抑制心室重构抗心力衰竭基础与临床研究证据,Ventricular Remodeling after Infarction and in Diastolic and Systolic Heart Failure,Jessup et al.N Engl J Med 2003;348:2007-2018,Neurohormonal model of HF,McMurray J,Pfeffer MA.Circulation.2002;105:2099-106.,Primary targets of treatment in HF,Jessup M,Brozena S.N Engl J Med.
2、2003;348:2007-18.,气阳虚乏,脉络瘀阻,尿少水肿,络息成积心室重构、心脏扩大,气虚不能运血,阳虚不能化水,“气分”（神经体液调节异常）,“水分”（钠水滁留）,“血分”（血流动力学异常）,益气温阳黄芪、附子、人参、桂枝,活血通络丹参、红花,利水消肿 葶苈子、泽泻、香加皮,标,本,兼治,强心、利尿、扩血管缓解心慌气短、不能平卧、尿少水肿症状,抑制RASS与交感神经减少心室重构,与RASS、交感神经系统激活导致心室重构为慢性心衰病机新概念相吻合,脉络学说指导慢性心衰病机、有效组方及作用研究,Cellular Immunology 2009,260:52-55,Results,The
3、effect of Qiliqiangxin on the echocardiographic and hemodynamic parameters in the infarcted hearts.,4 g/kg/day for 4 weeks for Rats,The ratio of TNF-a/IL-10 in infarcted myocardial tissue was reversed by Qiliqiangxin.,Conclusion:Qiliqiangxin improves cardiac function of rats with MI through regulati
4、on the balance between TNF-a and IL-10.,J Cardiovasc Pharmacol,2012,59(3):268-280,Conclusion:1.QL inhibits myocardial inammation and cardiomyocyte death and promotes cardiomyocyte proliferation,leading to an ameliorated cardiac remodeling and function in a mouse model of pressure overload.2.The poss
5、ible mechanisms may involve inhibition of angiotensin II type 1 receptor and activation of ErbB receptors.,American journal of hypertension,2012,25,250-260,QL:0.6mg/kg/day for 4 weeks for mice,Conclusion:1.QLQX improves both systolic and diastolic cardiac function in SHRs.2.QLQX downregulate the car
6、diac chymase signaling pathway and chymase-mediated ang II production.,临床试验注册,Li X,Zhang J,Huang J,Ma A,Yang J,Li W,Wu Z,Yao C,Zhang Y,Yao W,Zhang B,Gao R.A Multicenter,Randomized,Double-Blind,Parallel-Group,Placebo-Controlled Study of the Effects of Qili Qiangxin Capsules in Patients With Chronic H
7、eart Failure.J Am Coll Cardiol.2013;62(12):1065-1072.,临床研究简介,Li X,Zhang J,Huang J,Ma A,Yang J,Li W,Wu Z,Yao C,Zhang Y,Yao W,Zhang B,Gao R.A Multicenter,Randomized,Double-Blind,Parallel-Group,Placebo-Controlled Study of the Effects of Qili Qiangxin Capsules in Patients With Chronic Heart Failure.J Am
8、 Coll Cardiol.2013;62(12):1065-1072.,BNP/NT-proBNP可用于指导心衰的治疗,心衰患者治疗后BNP/NT-proBNP与基线相比下降达到或超过30%，表明治疗奏效如未下降或下降未达标甚至继续走高，则表明治疗效果不佳，应继续增强治疗的力度。,中国心力衰竭诊断和治疗指南2014 中华心血管病杂志 2014(42):2,2013 ACCF/AHA HF Guideline 生物标志物测定建议,GDMT,Guideline-Directed Medical Therapy;指南导向药物治疗2013 ACCF/AHA Guideline for the Man
9、agement of Heart Failure.E-Published on June 5,2013,available at:http:/content.onlinejacc.org/article.aspx?doi=10.1016/j.jacc.2013.05.019 a,Study Design,NT-proBNP的水平变化及下降超过30%的比例,两组NYHA心功能分级描述和比较,LVEF、LVED、6MWD基线与第12周随访变化趋势,明尼苏达生活质量量表评分变化趋势,心血管复合事件,药物不良事件,Editorial Comment Cardiotonic Modulation in
10、Heart Failure:Insights from Traditional Chinese Medicine 让衰竭的心脏更加强劲-中国传统医学给我们的启示,Tang WH,Huang Y.Cardiotonic Modulation in Heart Failure:Insights from Traditional Chinese Medicine.J Am Coll Cardiol.2013;62(12):1073-1074.,Editorial Comment（述评）-by Tang WHW,Huang Y,It is conceivable that in the future
11、if qili qiangxin proves to provide morbidity and mortality benefits in rigorous clinical trials,it will fundamentally challenge the existing foundation of scientific inquiry based upon the precise understanding of pharmacodynamics of drug therapies.可以想象的是，如果芪苈强心胶囊在未来高质量的临床研究中提供更多关于其对受试者发病率、死亡率益处的证据，
12、那么它将从根本上挑战现有的关于药物效应动力学研究的科学观念。,Tang WH,Huang Y.Cardiotonic Modulation in Heart Failure:Insights from Traditional Chinese Medicine.J Am Coll Cardiol.2013;62(12):1073-1074.,Editorial Comment（述评）-by Tang WHW,Huang Y,Yet even at present,the promising results reported by Li and colleagues may have alread
13、y opened the opportunity to explore with the latest technologies how synergistic interactions among active TCM ingredients can benefit the syndrome of heart failure.This is a challenge that we should all warmly embrace.现如今，这项富有前景的研究表明李及他的研究同事们已经打开了一扇如何利用最新科技研究传统中药活性成分在心力衰竭治疗中协同作用的大门。这是一个挑战，对此我们应该热烈拥
14、抱。,Tang WH,Huang Y.Cardiotonic Modulation in Heart Failure:Insights from Traditional Chinese Medicine.J Am Coll Cardiol.2013;62(12):1073-1074.,临床研究证据级别：由高到低,1.随机对照研究2.前瞻性非随机对照研究3.回顾性对照研究4.非对照研究或历史对照研究5.荟萃分析6.病例报道 7.评论，教授或其他专家意见 Professor Joseph S.Alpert Editor-in-Chief,American Journal of Medicine 2
15、013.7.19 Nanjing,中国心力衰竭诊断和治疗指南2014（中华心血管病杂志 2014(42):2）对芪苈强心临床试验结果进行了描述（参考文献58）,Working model:AMI remodeling,Our work:（我们的研究）Project1:Traditional Chinese Medication Qiliqiangxin attenuates cardiac remodeling after acute myocardial infarction in mice,Unpublished data,Results,Unpublished data,Unpublis
16、hed data,Unpublished data,Reversal experiments-PPARa PPARg,Unpublished data,Unpublished data,Unpublished data,Future work,Acute phase,Remodeling phase,Unpublished data,Unpublished data,Acute phase(TTC Staining),Figure 11,A,B,B,C,Project2:The matabolic effects of QLQX on H9C2(in vitro),Unpublished da
17、ta,Basal Oxidative Metabolism,Peak Oxidative Metabolism,Figure1:Oxidative Metabolism indicated by oxygen consumption of H9C2 myocytes treated with QL at different time and dose,A,Mitochondrial Uncoupling,Metabolic Reliance,B,C,Basal Glycolysis,Peak Glycolysis,Figure2:Glycolysis Metabolism indicated
18、by oxygen consumption of H9C2 myocytes treated with QL at different time and dose,A,B,Figure3:Mitochondrial Content measured by microscopy and flow cytometry,B,待发表文章:Traditional Chinese Medication Qiliqiangxin attenuates cardiac remodeling after acute myocardial infarction targeting PPARR已于3月31号向哈佛大
19、学医学院附院心内科主任、新英格兰副主编托尼教授汇报过研究结果受到好评。临床意义 作为预防心肌梗死后心室重构导致心衰的治疗策略之一？（B阶段）（RAS/BB）,Qiliqiangxin in Heart FailUre：AssESsment of Reduction in MorTality,Prof Xinli LiThe First Affiliated Hospital with Nanjing Medical Universityon behalf of the Investigators,Study Design,Therapeutic regimen:enrolled patient
20、s with HF are given oral medication treatment according to Diagnosis and Treatment Guidelines of HF(version 2014).Treatment group and control group add Qiliqiangxin capsule/placebo(4 capsules Tid)respectively on the basis of original medication.,screening,1,2,3,4,5,6,7,8,9,10,randomization,Visit,Tim
21、e(Month),-0.5,0,3,6,9,12,18,24,30,36,SHF case（n=1840 1:1）,DHF case（n=1840 1:1）,Mid-term evaluation of the follow-up in 36 months is made by statisticians unconnected with the trial.If the endpoint indicator is positive,the trial would be terminated.,Enrollment,42,48,11,12,observation period:3-4 years,The primary endpoint:composite endpoint of cardiovascular death and re-hospitalization for worsening heart failure,谢 谢！,
