摘要
目的观察血管紧张素Ⅱ（AngⅡ）激活p38MAPK和JNK在恢复失血性休克血管反应性中的作用。方法采用大鼠失血性休克模型（SD大鼠80只,体质量200-230g,雌雄各半）,观察AngⅡ处理对休克大鼠肠系膜上动脉（superior mesenteric artery,SMA）血管组织中p38MAPK和JNK的活性变化的影响,并用p38MAPK和JNK的特异性拮抗剂SB203580和SP600125,观察阻断p38MAPK和JNK对AngⅡ诱导的失血性休克血管反应性保护作用的影响。结果失血性休克大鼠肠系膜血管组织中p38MAPK的活性呈休克早期升高、休克晚期降低的趋势,在休克后0.5h和2h时p38MAPK的活性分别为正常对照的201.2%和53.2%（P〈0.01）;而JNK的活性水平随休克时间的延长而逐渐升高,休克2h时活性升为正常对照的308.8%（P〈0.01）。在休克晚期给予AngⅡ处理能明显升高休克血管p38MAPK和JNK活性水平,同时AngⅡ处理也升高了休克晚期肠系膜动脉血管的收缩反应性。p38MAPK的拮抗剂SB203580和JNK的拮抗剂SP600125均可拮抗AngⅡ诱导的p38MAPK和JNK激活,p38MAPK和JNK的活性分别降低为AngⅡ组的52.9%和44.8%（P〈0.05-0.01）;同时p38MAPK和JNK的拮抗剂也抑制了AngⅡ升高休克血管反应性的作用,使其分别降低为AngⅡ组的60.5%和65.0%（P〈0.01）。结论 p38MAPK和JNK参与AngⅡ对休克血管反应性的保护作用。
Objective To observe the role of angiotensin Ⅱ（AngⅡ）-activated p38 MAPK and JNK in vascular protective responses following hemorrhagic shock in rats.Methods Eighty SD rats with hemorrhagic shock（40 males and 40 females）,weighing 200 to 230 g,were enrolled in this study.Effect of AngⅡ on the activity of p38 MAPK and JNK was observed in superior mesenteric artery（SMA）of rats after hemorrhagic shock.Effects of AngⅡ-activated p38 MAPK and JNK on vascular protective responses after hemorrhagic shock in rats were observed using the p38 MAPK and JNK antagonists（SB203580 and SP600125）.Results The activity of p38 MAPK was increased after early hemorrhagic shock and then decreased after late hemorrhagic shock.The activity of p38 MAPK was 201.2% and 53.2% higher in rats with hemorrhagic shock than in normal controls at 0.5 h and 2 h after hemorrhagic shock,respectively（P0.01）.The activity of JNK was increased with the prolongation of hemorrhagic shock,which was 308.8% higher in rats with hemorrhagic shock than in normal controls at 2 h after hemorrhagic shock（P0.01）.AngⅡ given at the late hemorrhagic shock could significantly increased the activity of p38 MAPK and JNK and the contractile response of SMA.SB203580 and SP600125 inhibited the AngⅡ-activated p38 MAPK and JNK activity,which was decreased to 52.9% and 44.8%,respectively（P0.05）,and suppressed the increased vascular reactivity due to AngⅡ-activated p38 MAPK and JNK,which was decreased to 60.5% and 65.0%,respectively（P0.01）.Conclusion p38 MAPK and JNK are involved in the effect of AngⅡ on vascular protective responses following hemorrhagic shock in rats.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2010年第21期2269-2272,共4页
Journal of Third Military Medical University
基金
国家重点基础研究发展计划(973计划)(2005CB522601)
国家自然科学基金重点项目(30830053)
国家自然科学基金青年基金(30901559)
教育部创新团队资助计划(IRT0712)
第三军医大学科研基金(2008XG136)~~
