血管生成素-1，2经p38丝裂原活化蛋白激酶调节失血性休克血管低反应性  

Ang 1 and Ang 2 regulate the vascular hyporeactivity through p38MAPK in the late period ofhemorrhagic shock in rats

作　　者：徐竞[1] 李涛 杨光明[1] 刘良明[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所二室,重庆400042 [2]创伤、烧伤与复合伤国家重点实验室,重庆400042

出　　处：《中国急救医学》2012年第3期218-222,共5页Chinese Journal of Critical Care Medicine

基　　金：国家自然科学基金项目（No.30801189）;重庆市自然科学基金项目（CSTC,No.2008BB5103）

摘　　要：目的观察p38丝裂原活化蛋白激酶（p38MAPK）在血管生成素-1（Ang-1）、血管生成素-2（Ang-2）调节失血性休克大鼠血管反应性双相变化中的作用。方法观察失血性休克后不同时问点肠系膜上动脉（SMA）中p38MAPK蛋白表达和磷酸化变化，p38MAPK抑制剂对Ang-1和Ang-2调节缺氧早期和晚期血管反应性作用的影响，以及给予Ang-1、Ang-2和Tie-1抑制剂后缺氧血管内皮细胞（VEC）和血管平滑肌细胞（VSMC）混合细胞中p38MAPK蛋白表达和磷酸化变化。结果失血性休克后p38MAPK磷酸化水平显著增高；p38MAPK抑制剂可显著改善缺氧4h血管低反应性并拮抗Ang-2进一步降低缺氧4h血管低反应性的作用；Ang-1和Tie-2抑制剂可显著抑制缺氧4h的p38MAPK磷酸化增高（P〈0，01）。结论p38MAPK参与了Ang-t和Ang-2对休克晚期血管低反应性的调节，但不是休克早期血管高反应性的主要调节分子。To observe the role of p38 mitogen activated protein kinase （p38MAPK） in the biphasic change of vascular reactivity regulated by angiopoietin 1 （Ang 1 ） and angiopoietin 2 （Ang 2 ） after hemorrhagic shock in rats. Methods The protein expression and phosphorylation of p38MAPK in the superior mesenteric artery （SMA） after hemorrhagic shock were measured by Western Blotting technique, the effect of p38MAPK inhibitor on the vascular reactivity of SMA in the early （ hyper reactivity） and late （ hyporeactivity） period of hypoxia when treated with Ang 1 and Ang 2 were observed by the isolated organ perfusion system, and the protein expression and phosphorylation of p38MAPK in the hypoxia mixture of vascular endothelial cell （VEC） and vascular smooth muscle cell （VSMC） when treated with Ang 1 and Ang 2 were measured by Western Blotting technique. Results The phosphorylation of p38MAPK increased significantly after hemorrhagic shock （P 〈 0.01 ）. p38MAPK could recover the vascular reactivity after 4 h hypoxia, and repress the decrease effect of Ang 2 on vascular reactivity after 4 h hypoxia. At 4 h hypoxia, Ang 1 and Tie 2 inhibitor could decrease the phosphorylation of p38MAPK （P 〈 0. 01 ）. Conclusion p38MAPK contributes to the regulation of Ang 1 and Ang 2 in the vascular hyporeactivity in the late period of hemorrhagic shock, while did not participated in the regulation of vascular hyperreactivity in the early shock.

关 键 词：失血性休克 血管反应性 双相变化 血管生成素-1 血管生成素-2 p38丝裂原活化蛋白激酶(p38MAPK) 

分 类 号：R364.12[医药卫生—病理学]