【作者】 龙石银；

【导师】 傅明德；

【作者基本信息】 四川大学 ， 生物化学与分子生物学， 2006， 博士

【摘要】 第一部分 研究背景：动脉粥样硬化(artherosclerosis，As)病程复杂，涉及到内皮损伤，粘附分子表达增强，血小板附着血管壁，单核淋巴细胞粘着渗入到动脉壁，促炎细胞因子出现，LDL的氧化和浸润，单核细胞增生、迁移、活化，巨噬细胞和平滑肌泡沫化等。目前对As发病机理已提出众多学说，主要有脂肪浸润学说、血小板聚集和血栓形成学说、平滑肌细胞克隆学说和损伤反应学说。近年来研究发现，As的病理表现具有炎症病理的基本表现形式，随着炎症细胞和炎症介质在动脉粥样硬化斑块中的不断检出，越来越多的研究结果支持As不单纯是内皮损伤后被动的脂质浸润或修复过程，更重要的是一种活跃的炎症性疾病。许多证据表明心理应激是心血管疾病的危险因子，心理社会因素参与一部分心血管疾病如As的起病和进程，心血管疾病与心理社会因素之间的关联日益引起重视，但其生物学机制并不十分清楚。 应激是内环境稳态受到威胁的状态，当机体受到环境、心理、生理性应激原等的刺激时均可以引起机体的应激反应，激活交感神经系统(sympathetic nervous system，SNS)和下丘脑-垂体-肾上腺轴(hypothalamic-pituitary-adrenal axis，HPA)产生相应的生理学变化。在易感者或高危人群中，反复的急性应激或者慢性应激激活SNS、HPA等可引起儿茶酚胺类激素、皮质类固醇等一系列的应激性激素的释放，结果导致心血管反应性增高，改变血流和血压导致内皮损伤和血小板附壁；细胞因子和其它因子诱导功能异常的内皮细胞表达粘附分子，募集单核淋巴细胞粘着进入内膜。反复的急性应激或者慢性应激也可激活单核细胞、肥大细胞等，产生细胞因子和炎性介质等可加重炎症反应。即应激时的皮质类固醇和儿茶酚胺类激素实际上启动了和炎症反应相似的调节机制，如生成细胞因子和急性期反应物质，心理性刺激触发的应激反应涵盖了炎性反更多还原

【Abstract】 Part OneBackground: The atherosclerotic process is the culmination of a number of events: endothelial injury; induction of adhesion molecules; adherence of platelets; recruitment of monocytes and lymphocytes which adhere to and permeate the arterial wall; appearance of proinflammatory cytokines; infiltration and oxidation of low-density lipoprotein; activation, movement, and hyperplasia of myocytes; formation of foam cells from macrophages and smooth muscle cells. One of the focuses of cardiovascular disease research is to study pathogenesis of atherosclerosis (As). At present, there are many theories about the pathogenesis of As, such as the fat infiltration theory, blood platelet aggregation and thrombosis theory, smooth muscle cellular clone theory and damage reaction theory. It is discovered in recent years that the pathological performance of As featured the basic form of inflammatory pathology. Along with continuous finding of inflammatory cells and media in atheromatous plaque, atherosclerosis has come to be recognized as active and inflammatory rather than simply a passive process of lipid infiltration or a reparative process after endothelial injury. Recently, many studies have demonstrated that psychosocial stress is a risk factor for cardiovascular disease. A large body of evidence, which indicates that psychosocial factors play some role in the etiology and progression of certain cardiovascular diseases such as atherosclerosis, has now been更多还原