血管内压力升高致血管壁氧张力改变与动脉粥样硬化形成机制的研究  

Hypertension activates vessel wall oxygen and metabolism sensing pathways and accelerates atherosclerosis

作　　者：蒋卫东[1] 秦爱琼[1] 刘玉胜[1] 王欣[1] 鹿庆华[1] 葛志明[2] 

机构地区：[1]山东大学第二医院心内科,济南250033 [2]山东大学齐鲁医院心内科

出　　处：《中华老年医学杂志》2012年第12期1103-1107,共5页Chinese Journal of Geriatrics

基　　金：山东省自然科学基金（Y2006C59）;山东省优秀中青年科学家科研奖励基金（2007BS03046）;山东省卫生厅中医管理局（2011-209）

摘　　要：目的探讨血管内压力升高致动脉粥样硬化发生、发展的分子机制。方法对载质蛋白E基因敲除（ApoE-）小鼠行跨主动脉缩窄术后正常饮食，观察缩窄术上、下血管段动脉粥样硬化斑块形成情况，并应用肌动描记系统体外不同压力灌注小鼠颈动脉血管段，观察承受不同灌注压力血管段缺氧诱导因子-1α（HIF-1α）及其下游血红素氧和酶（HO-1）和活性氧的表达水平变化；免疫印迹（Westernblot）检测腺苷酸活化蛋白激酶（AMPK）、磷酸化腺苷单磷酸活化蛋白激酶（p-AMPK）水平。结果ApoE小鼠正常饮食，跨主动脉缩窄术所引起的血流动力学改变，可造成缩窄上游血管段动脉粥样硬化斑块形成，而下游血管段无动脉粥样硬化斑块形成。体外高压力灌注血管段血管壁HIF-1α表达水平增高，且其下游HO-1表达水平较低压力灌注血管段增高（2．7±0．6）倍（P〈0．05）；活性氧表达水平、p-AMPK水平增高（均P〈0．05）。结论动脉压力导致血管壁氧张力降低，HIF-1α和AMPK途径激活是血管内压力升高致动脉粥样硬化形成的重要机制之一。Objective To study the molecular mechanism of atherosclerosis induced by intravascular pressure. Methods Technic aortic coarctation （TAC） was performed in ApoE-/-mice （n=8） and control littermate （n=8） mice. HE staining was performed in the vessels upstream and downstream of the mice models. In vitro, hypoxia-inducible factor-la （HIF-la）, heme oxygenase, reactive oxygen species and phosphorylated AMP activated protein kinase （AMPK） were analyzed in different intravascular pressure with a myograph system that allowed independent variation of flow and pressure. Results After one month of TAC, ApoE-/- mice in a normal chow diet developed occlusive plaque and accelerated atherosclerotic lesions exclusively in upstream high-pressure vessel segments. In vitro, HIF-1α was increased, heine oxygenase was higher over （2.7 -- 0.6） fold, reactive oxygen species and phosphorylated AMPK were also enhanced in high intravascular pressure perfused vessel segments as compared with low intravascular pressure perfused vessel segments （all P（0.05）. Conclusions Intravascular pressure elevation can activate hypoxia and metabolism-associated pathways in the arterial wall, and predispose atherosclerosis accelerated.

关 键 词：高血压 缺氧诱导因子1 Α亚基 AMP-活化蛋白激酶 动脉硬化 

分 类 号：R543.5[医药卫生—心血管疾病]