動(dòng)脈粥樣硬化的發(fā)生機(jī)制

1、v脂質(zhì)浸潤(rùn)學(xué)說(shuō)脂質(zhì)浸潤(rùn)學(xué)說(shuō)v血小板聚集和血栓形成學(xué)說(shuō)血小板聚集和血栓形成學(xué)說(shuō)v平滑肌細(xì)胞克隆學(xué)說(shuō)平滑肌細(xì)胞克隆學(xué)說(shuō)v損傷反應(yīng)學(xué)說(shuō)損傷反應(yīng)學(xué)說(shuō) University of University of California, California, USAUSA脂質(zhì)浸潤(rùn)學(xué)說(shuō)脂質(zhì)浸潤(rùn)學(xué)說(shuō)LIPID HYPOTHESISLIPID HYPOTHESISUniversity of University of Washington,USAWashington,USA損傷反應(yīng)學(xué)說(shuō)損傷反應(yīng)學(xué)說(shuō)RESPONSE-TO-INJURY RESPONSE-TO-INJURY HYPOTHESISHYPOTHESISH

2、arvard Medical Harvard Medical School, USASchool, USA炎癥學(xué)說(shuō)炎癥學(xué)說(shuō)INFLAMMATION HYPOTHESISINFLAMMATION HYPOTHESIS動(dòng)脈粥樣硬化的慢性炎癥進(jìn)程正常動(dòng)脈內(nèi)膜結(jié)構(gòu)正常動(dòng)脈內(nèi)膜結(jié)構(gòu)大型彈力型動(dòng)脈大型彈力型動(dòng)脈 中型肌彈力動(dòng)脈中型肌彈力動(dòng)脈Steinberg D, et al. N Engl J Med. 1989;320:915-924.LDL沉積于動(dòng)脈內(nèi)膜下沉積于動(dòng)脈內(nèi)膜下幾個(gè)關(guān)鍵點(diǎn)幾個(gè)關(guān)鍵點(diǎn) 內(nèi)皮細(xì)胞通透性?xún)?nèi)皮細(xì)胞通透性 顆粒直徑顆粒直徑 50- 80mg/dL 內(nèi)皮下基質(zhì)的特性?xún)?nèi)皮下基質(zhì)的特性 S

3、teinberg D, et al. N Engl J Med. 1989;320:915-924.LDL的修飾的修飾LDLLDL氧化氧化n巨噬細(xì)胞巨噬細(xì)胞n內(nèi)皮細(xì)胞內(nèi)皮細(xì)胞n 平滑肌細(xì)胞平滑肌細(xì)胞n髓過(guò)氧化酶髓過(guò)氧化酶n脂氧化酶脂氧化酶n還原型輔酶還原型輔酶 II II氧化酶氧化酶（NADPH NADPH ）Charo IF. Curr Opin Lipidol. 1992;3:335-343.黏附分子黏附分子Charo IF. Curr Opin Lipidol. 1992;3:335-343.趨化因子趨化因子Steinberg D, et al. N Engl J Med. 1989;3

4、20:915-924.巨噬細(xì)胞Daniel S, et al. Nature Medicine. 2002 Nov; 8(11):1211-7Steinberg D et al. N Engl J Med 1989;320:915-924.（ Foam Cell ）Miyazaki A, et al. Biochim Biophys Acta. 1992;1126:73-80.Ross R. N Engl J Med. 1999;340:115-126.趨化因子趨化因子動(dòng)脈粥樣硬化脂紋期動(dòng)脈粥樣硬化脂紋期內(nèi)皮下聚集的大量泡沫細(xì)胞內(nèi)皮下聚集的大量泡沫細(xì)胞Ross R. N Engl J Med. 1999;340:115-126.中膜中膜細(xì)胞外基質(zhì)細(xì)胞外基質(zhì)膠原膠原纖維纖維蛋白多糖蛋白多糖彈力蛋白彈力蛋白 Libby P. Circulation 1995;91:2844-2850.+合成合成降解降解脂核脂核TNF- MCP-1M-CSF纖維帽纖維帽CD-40L 基質(zhì)降解酶 膠原酶膠原酶 金屬蛋白酶金屬蛋白酶 彈性蛋白酶巨噬細(xì)胞巨噬細(xì)胞氨基酸氨基酸T-淋巴細(xì)胞淋巴細(xì)胞氨基酸氨基酸膠原膠原彈力纖維彈力纖維動(dòng)脈粥樣硬化的慢性炎癥進(jìn)程1 1期期 初始病變初始病變 2 2期期 脂質(zhì)條紋