Abstract:
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.