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|本期目录/Table of Contents|

兔颈动脉外膜损伤术后氧化应激中p38 MAPK的表达变化

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2009年第5期
页码:
615-620
栏目:
基础研究
出版日期:
2009-07-14

文章信息/Info

Title:
Expression of p38 MAPK in oxidative stress response to rabbit carotid adventitial injury
作者:
高琳; 汤月霞; 姚睿荣; 梁春; 任雨笙; 潘晓明; 吴宗贵
第二军医大学附属长征医院心内科，上海 200003
Author(s):
GAO Lin;  TANG Yue-xia;  YAO Rui-rong;  LIANG Chun;  REN Yu-sheng;  PAN Xiao-ming;  WU Zong-gui
Department of Cardiology, Second Hospital, Second Military Medical University, Shanghai 200003, China
关键词:
血管外膜; 损伤; 活性氧物质; p38 MAPK; 动脉粥样硬化
Keywords:
adventitia;  injury;  reactive oxygen species;  p38 MAPK;  atherosclerosis
分类号:
R543.4
DOI:
-
文献标识码:
A
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。
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.

参考文献/References

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［4］ Son YH, Jeong YT, Lee KA, et al. Roles of MAPK and NF-kappaB in interleukin-6 induction by lipopolysaccharide in vascular smooth muscle cells［J］. J Cardiovasc Pharmacol, 2008, 51(1):71-77.

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［7］ Matsumoto-Ida M, Takimoto Y, Aoyama T, et al. Activation of TGF-beta1-TAK1-p38 MAPK pathway in spared cardiomyocytes is involved in left ventricular remodeling after myocardial infarction in rats［J］. Am J Physiol Heart Circ Physiol, 2006, 290(2):H709-H715.

［8］ Chen YX, Ma X, Whitman S, et al. Novel antiinflammatory vascular benefits of systemic and stent-based delivery of ethylisopropylamiloride［J］. Circulation, 2004, 110(24):3721-3726.

［9］ Takayama T, Wada A, Tsutamoto T, et al. Contribution of vascular NAD(P)H oxidase to endothelial dysfunction in heart failure and the therapeutic effects of HMG-CoA reductase inhibitor［J］. Circ J, 2004, 68(11):1067-1075.

［10］Mallawaarachchi CM, Weissberg PL, Siow RC. Antagonism of platelet-derived growth factor by perivascular gene transfer attenuates adventitial cell migration after vascular injury: new tricks for old dogs?［J］. FASEB J, 2006, 20(10):1686-1688.

备注/Memo

备注/Memo:
收稿日期：2008-6-19.基金项目：国家重点基础研究规划项目973课题资助（2005CB523309） 通讯作者：吴宗贵，教授，主要从事动脉粥样硬化方面研究Email：zgwu@medmail.com.cn 作者简介：高琳，硕士生Email：cutegaolin@163.com
更新日期/Last Update: 2009-07-22