兔颈动脉外膜损伤术后氧化应激中p38 MAPK的表达变化  

Expression of p38 MAPK in oxidative stress response to rabbit carotid adventitial injury

作　　者：高琳[1] 汤月霞[1] 姚睿荣[1] 梁春[1] 任雨笙[1] 潘晓明[1] 吴宗贵[1] 

机构地区：[1]第二军医大学附属长征医院心内科,上海200003

出　　处：《心脏杂志》2009年第5期615-620,共6页Chinese Heart Journal

基　　金：国家重点基础研究规划项目973课题资助(2005CB523309)

摘　　要：目的:探讨p38 MAPK在兔颈动脉外膜损伤致内膜病变氧化应激中的作用。方法:采用高脂饮食喂养及胶原酶消化+机械分离的方法,建立兔颈动脉外膜损伤致内膜病变的模型。测定术后不同时间点,对照组和阿托伐他汀组家兔血脂指标(TC,TG,LDL-C和HDL-C)、新生内膜面积(NIA)、活性氧物质(ROS)的产生情况,观察磷酸化p38 MAPK的表达及定位。结果:从颈动脉外膜损伤术后1 d始,ROS的产生和磷酸化p38 MAPK的表达即增加并持续至少28 d。阿托伐他汀干预后,与对照组比较,各时间点ROS的产生及磷酸化p38的表达均下调(P<0.05),TC及LDL-C的水平下降(P<0.05),新生内膜形成减少(P<0.05)。结论:氧化应激水平的升高和p38MAPK的持续激活,是血管外膜损伤致新生内膜形成的可能机制之一。AIM： To investigate the role of p38 mitogen-activated protein kinase （MAPK） in oxidative stress response to intimal lesion induced by rabbit carotid adventitial injury. METHODS： A model of intimal lesion induced by rabbit carotid adventitial injury was set up with collagenase digestion and mechanical dissection in bypercholesterolemie rabbits. Blood biochemical tests [ total cholesterol （TC） , triglyceride （TG）, low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） ], neointimal area （NIA）, production of reactive oxygen species （ROS） and expression and location of phospho-p38 MAPK were analyzed at different time points after carotid adventitial injury in both control group and atorvastatin group. RESULTS： ROS production and p38 MAPK activation were observed at 1 day after carotid adventitial injury and remained elevated for at least 28 days. Long-term treatment （4 weeks） with HMG-CoA reductase inhibitor atorvastain reduced the vascular response to carotid adventitial injury in hypereholesterolemic rabbits, decreased TC and LDL-C, and alleviated intimal hyperplasia compared with those in control group （P 〈 0. 05 ）. CONCLUSION： Increased production of ROS and the sustained activation of p38 MAPK play an important role in the formation of neointima induced by carotid adventitial injury.

关 键 词：血管外膜 损伤 活性氧物质 P38 MAPK 动脉粥样硬化 

分 类 号：R543.4[医药卫生—心血管疾病]