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.
出处
《心脏杂志》
CAS
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)