动脉粥样硬化斑块逆转的治疗和挑战教学文稿.doc

动脉粥样硬化斑块逆转的治疗和挑战教学文稿 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 JCardiol.1998;82(suppl10A):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 SteeringCommittee.Lancet1996;348:1329-1339?动脉粥样硬化斑块?能逆转?还是不能逆转?挑战PAS三联的组成P robucolA spirinS 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?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8LDL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9血中胆固醇由由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.xxNov;8 (11):1211-7LDL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TXA2血栓血小板聚集Pollack CV,et al.The Journal of EmergencyMedicine.xx (34)4:417-42835X109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PGH2PGC2TXA2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 studyon PAStherapyxx-xx,CHD wereselected bycoronary angiographyor coronaryCTA.All cases were dividedinto twogroups;control group65(AS)aspirin100mg/d and,Atrovastatin20mg/d.PAS group85(APS)probucol,0.5g/d,aspirin100mg/d andAtrovastatin20mg/d.And allcaseswerefollowed up for1year,examined thecoronary plaque reversal throughCoronary angiographyor coronaryCTA0.50.510.520.530.540.550.560.570.58血管狭窄程度治疗前治疗后AS group(65case)Comparison ofvascular plaquestenosis beforeand aftertherapy（xs，mm）indicators Beforetherapy aftertherapy difference（d）t pVascular stenosis0.68士0.180.53士0.190.15士0.113.13p0.01In AS group,vascular stenosiswas decreasedby about15%after treatment.00.10.20.30.40.50.60.70.8血管狭窄程度治疗前治疗后PASgroup（84case）Comparison ofvascular plaquestenosis beforeand aftertherapy（xs，mm Xs）indicators Beforetherapy aftertherapy difference（d）t pVascular stenosis0.71士0.250.47士0.410.24士0.194.59p0.01In PAS group,vascular stenosiswas decreasedby24%after treatment.00.050.10.150.20.25血管狭窄程度AS组PAS组Comparison ofvascular plaquestenosis ASand PAStherapy（Xs）indicators ASgroup PASgroup（d）t pVascular stenosis0.15士0.110.24士0.190.09士0.243.76p0.01Comparing PASgroup andASgroup,PASgrouphad more9%plaque reversalPlaque 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=31Atrovastatin10mg,Qd P组n=30Probucol250mg,Bid A+P组n=31Atrovastatin10mg,Qd+Probucol250mg,Bid疗程8周【试验发布】日本68届循环年会报告【研究单位】Tadateru TakayamaNihon UniversitySchool 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 on68th ScientificSessions ofJapanese CirculationSociety.Mar27-29,xx,Tokyo,Japan.30*P=NS90*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research unitDepartment ofCardiovascular Medicine,Osaka UniversityGraduate SchoolofMedicine,Japan.【study designmulti-centered,randomised,case-control study410patients withFH wererandomisely groupedinto probucol group(307cases),non-probucolgroup(103cases)Follow-upfor15years(average),20years(maximum)Study time:1984-xxindicatorscardiovascular events:include acutemyocardial infarction,pectoris angina,heart failure,TIA oratherosclerosis inducedperipheral arterialdisease Probucol,secondary preventionfor cardiovascularevents inhigh riskpatients Journalof Atherosclerosis and Thrombosis,xx;15:292-303.POSITIVE研究Probucol,effective decreasein cardiovascularevents之乐?组非之乐?组HR=0.13（0.05-0.34）P0.001100806040xx0501520未出现事件患者百分比随访时间%（年）JournalofAtherosclerosisandThrombosis,xx;15:292-303.POSITIVE研究?Although PAStherapy broughtus goodprospectus.?But westill havesome problemsto investigate.?Such as:Why binationtherapy ofatorvastatin andantioxidants makeeffects inplaquereversal?what isthe