兔颈动脉外膜损伤术后氧化应激中p38 MAPK的表达变化

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p38 MAPK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。

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

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 hypercholesterolemic 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 hypercholesterolemic 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.