动脉粥样硬化斑块逆转治疗和挑战25张课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,动脉粥样硬化斑块逆转治疗和挑战,1、舟遥遥以轻飏，风飘飘而吹衣。,2、秋菊有佳色，裛露掇其英。,3、日月掷人去，有志不获骋。,4、未言心相醉，不再接杯酒。,5、黄发垂髫，并怡然自乐。,动脉粥样硬化斑块逆转治疗和挑战动脉粥样硬化斑块逆转治疗和挑战1、舟遥遥以轻飏，风飘飘而吹衣。,2、秋菊有佳色，裛露掇其英。,3、日月掷人去，有志不获骋。,4、未言心相醉，不再接杯酒。,5、黄发垂髫，并怡然自乐。动脉粥样硬化斑块逆转的治疗和挑战 吉林大学第二医院心内科,孟晓萍动脉粥样硬化伴随一生的风险泡沫细胞脂纹中期损伤粥样硬化纤维斑块复合性病变/破裂内皮功能失调10岁开始30岁开始40岁开始脂质沉积为主平滑肌细胞和胶原血栓出血Pepine CJ.Am J Cardiol.1998;82(suppl 10A):23S-27S.,动脉粥样硬化斑块逆转的治疗和挑战,吉林大学第二医院心内科,孟晓萍,动脉粥样硬化,伴随一生的风险,泡沫细胞,脂纹,中期损伤,粥样硬化,纤维斑块,复合性病变,/,破裂,内皮功能失调,10,岁开始,30,岁开始,40,岁开始,脂质沉积为主,平滑肌细胞和胶原,血栓出血,Pepine CJ.Am J Cardiol.1998;82(suppl 10A):23S-27S.,动脉粥样硬化累及全身血管床,冠状动脉疾病,脑血管疾病,外周动脉疾病,3.8%,11.9%,3.3%,24.7%,19.2%,7.4%,29.9%,3.8%,11.8%,3.3%,CAPRIE Steering Committee.Lancet 1996;348:1329-1339,动脉粥样硬化斑块,能逆转,还是不能逆转,挑战,我们用PAS疗法挑战,抗氧化剂-普罗布考,抗血小板聚集-阿司匹林,降血脂-阿托伐他汀,来自动脉硬化的经典学说,PAS 三联的组成,P,robucol,A,spirin,S,tatins,汀类药物可以改善血管功能,，,降脂的功能,PAS疗法的理论基础,来自动脉硬化的经典学说,内皮损伤学说,氧化应激学说,血栓形成学说,9,LDL,内皮损伤,管腔,单核细胞,巨噬细胞,泡沫细胞,内膜,oxLDL,细胞增殖、退化,活性氧,ROS,SR-A,脂核,在血管粘附分子-1(VCAM-1),和细胞间粘附分子-1(ICAM-1)的作用下，,粘附到血管内皮上；,单核细胞趋化蛋白,-1的介导下，穿越血管内皮细胞,10,血中,胆固醇,由,LDL携带运输,ox-LDL,结合慢,结合快,LDL-R,SR-A,表达减少功能下调,表达增加功能上调,Daniel S,et al.,Nature Medicine.,2002 Nov;8(11):1211-7,LDL颗粒被吞饮,然后进入溶酶体。在溶酶体中,LDL被水解释放出游离胆固醇。游离胆固 醇可掺入细胞浆膜中,被细胞膜所利用或转换成其他物质。而LDL受体则可再循环,细胞内游离的胆固醇增多抑制受体的合成和表达,细胞 内游离胆固醇含量增加则抑制,LDL受体的合成和表达,反之亦然。,LDL表面多不饱和脂肪酸双链断裂和ApoB,形成,共轭双烯,ROS活性氧簇,化学修饰,LDL-C,动脉粥样硬化,X,高血脂与动脉粥样硬化形成之间存在中间环节：化学修饰,内皮损伤诱发血栓形成示意图,胶原与,vWF因子结合,与糖蛋白（GPIb),血小板,激活,TXA,2,血栓,血小板,聚集,Pollack CV,et al.The Journal of Emergency Medicine.2008(34)4:417-428,35 X 10,9,血小板粘附在内皮细胞受损的胶原上，释放ADP和TXA2,然后引起血小板,激活、聚集，血栓形成。,粘附,磷脂酶,A2被激活,裂解,膜磷脂,游离花生四稀酸,环氧化酶,PGH2,PGC2,TXA2,血栓素合成酶,花生四烯酸途径,血小板释放内源性ADP,通过血小板膜上的ADP受体引起聚集,凝血酶IIa,凝血酶原II,纤维蛋白原,纤维蛋白,血小板间的聚集是两个血小板的膜,上糖蛋白纤维蛋白原暴露在,Ca2+参与,纤维蛋白原结合才能连接血小板,。,抑制血栓,的形成,抑制氧化的,LDL-C 的形成,减少OX-LDL,底物形成,抗氧化,抑制MMPs,降血脂,抗血小板,聚集,导致动脉粥样硬化心血管事件的三个主要环节,传统疗法,Our study on PAS therapy,2008-2011,CHD,were selected by coronary angiography or coronary CTA.,All cases were divided into two groups;,control group 65(AS)aspirin 100mg/d and ,Atrovastatin 20mg/d.,PAS group,85(APS)probucol,0.5g/d,aspirin100mg/d and Atrovastatin 20mg/d.And,all cases were followed up for 1 year,examined the coronary plaque reversal through Coronary angiography or c,oronary CTA,AS group,(65case),Comparison of vascular plaque stenosis before and after therapy（xs，mm）,indicators,Before,therapy,after therapy,difference（d）,t,p,Vascular,stenosis,0.68士0.18,0.53士0.19,0.15士0.11,3.13,p0.01,In AS group,vascular stenosis was decreased by about 15%after treatment.,PASgroup（,84case）,Comparison of vascular plaque stenosis,before and after therapy（xs，mm,Xs）,indicators,Before,therapy,after,therapy,difference,（d）,t,p,Vascular,stenosis,0.71士0.25,0.47士0.41,0.24士0.19,4.59,p0.01,In PAS group,vascular stenosis was decreased by 24%after treatment.,Com,parison of vascular plaque stenosis AS and,PAS therapy,（,Xs）,indicators,AS group,PAS group,（d）,t,p,Vascular,stenosis,0.15士0.11,0.24士0.19,0.09士0.24,3.76,p0.01,Comparing PAS group and AS group,PAS group had more 9%plaque reversal,Plaque reversal,吴世艳1.jpg,动脉粥样硬化,Probucol与他汀联合治疗对斑块稳定性的影响,【背景资料】,92名冠心病患者分别给予:A组 n=31 Atrovastatin 10mg,QdP组 n=30 Probucol 250mg,BidA+P组 n=31 Atrovastatin 10mg,Qd+Probucol 250mg,Bid 疗程8周,【试验发布】,日本68届循环年会报告,【研究单位】,Tadateru Takayama,Nihon University School of Medicine,Tokyo,Japan,probucol单用或与他汀联用均显著提高斑块稳定性,Tadateru T.,Presented on 68th Scientific Sessions of Japanese Circulation Society.,Mar 27-29,2004,Tokyo,Japan.,30*,P=NS,90*,*P0.05,与基线相比斑块回声强度增加比例,(%),更有效稳定斑块,之乐,组,(500mg/d),阿托伐他汀组,(10mg/d),之乐,+阿托伐他汀组,P+S,research unit,Department of Cardiovascular Medicine,Osaka University Graduate School of Medicine,Japan.,【,study design multi-centered,randomised,case-control study,410 patients with FH were randomisely grouped into,probucol group(307 cases),non-probucol group(103 cases),Follow-up for 15 years(average),20 years(maximum),Study time:1984-2005,indicators cardiovascular events:include acute myocardial infarction,pectoris angina,heart failure,TIA or atherosclerosis induced peripheral arterial disease,Probucol,secondary prevention for cardiovascular events in high risk patients,Journal of Atherosclerosis and Thrombosis,2008;15:292-303.,POSITIVE研究,Probucol,effective decrease in cardiovascular events,之乐,组,非之乐,组,HR=0.13（0.05-0.34）,P0.001,100,80,60,40,20,0,10,5,0,15,20,未出现事件患者百分比,随访时间,%,（年）,Journal of Atherosclerosis and Thrombosis,2008;15:292-303.,POSITIVE研究,Although PAS therapy brought us good prospectus.,But we still have some problems to investigate.,Such as:Why combination therapy of atorvastatin and antioxidants make effects in plaque reversal?what is the mechanism behind it?,We believe reversal of atherosclerotic plaque is not a mystery.It needs our continuity and hard work,24,lets all of us cooperate to challenge to atherosclerosis,Thanks for everybody attention,51,、天下之事常成于困约，而败于奢靡。,陆游,52,、生命不等于是呼吸，生命是活动。,卢梭,53,、伟大的事业，需要决心，能力，组织和责任感。,易卜生,54,、唯书籍不朽。,乔特,55,、为中华之崛起而读书。,周