细胞外信号调节激酶介导血管生成素-1、2对休克血管低反应性的调节  

Extracellular signal regulated kinase contributes to the regulation of angiopoietin-1 and -2 on the vascular hyporeactivity after hemorrhagic shock

作　　者：徐竞[1] 杨光明[1] 李涛[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创伤、烧伤与复合伤国家重点实验室,重庆400042

出　　处：《中华实验外科杂志》2012年第7期1290-1292,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（30801189）;重庆市自然科学基金资助项目（CSTC,2008BB5103）

摘　　要：目的观察细胞外信号调节激酶（Erk）在血管生成素，1（Ang-1）、血管生成素-2（Ang-2）调节失血性休克血管反应性双相变化中的作用。方法采用SD大鼠152只和混合培养的血管内皮细胞（VEC）、血管平滑肌细胞（VSMC），观察失血性休克后肠系膜上动脉（SMA）中Erk蛋白表达和磷酸化变化，Erk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抑制剂后缺氧混合细胞中Erk蛋白表达和磷酸化的变化。结果（1）失血性休克后SMA中Erk磷酸化逐渐增高，休克1h．2h和4h分别增高至正常对照组的2．72、3．32和3．46倍（P〈0．01）。（2）Erk抑制剂可恢复缺氧4h血管反府性并拮抗Ang-2（200μg/L）降低缺氧4h血管低反应性的作用，去甲肾上腺（NE）的最大收缩力（Emax）分别由5．875ran升高至9．681mN和由3．444mN增高至9．003mN（P〈0．01）。（3）Ang-1和Tie-2抑制剂可抑制缺氧4h的Erk磷酸化增高，使其由0．6258分别降低至0．2643和0．2578（P〈0．01）。结论Erk磷酸化介导休克晚期Ang-2降低血管反应性的调节作用。Objective To observe the role of extracellular signal regulated kinase （Erk） in the regulation of angiopoietin-1 （ Ang-1 ） and Ang-2 on the biphasic change of vascular reactivity after hemor- rhagic shock in rats. Methods The152 SD rats and mix-cultured vascular endothelial cells （VECs） and vascular smooth muscle cells （VSMCs） were adopted to observe the protein expression and tyrosine phos- phorylation of Erk in the superior mesenteric artery （SMA） after hemorrhagic shock, the effect of Erk in- hibitor on the vascular reactivity of SMA in the early （hyperreactivity） and late （hyporeactivity） period of hypoxia when treated with Ang-1 and Ang-2, and the protein expression and phosphorylation of Erk in the hypoxia cells mixture when treated with Ang-1 and Ang-2. Results （ 1 ） The phosphorylation of Erk was increased significantly after hemorrhagic shock, which was 2. 72, 3.32 and 3.46 times of normal control in shock 1-h, 2-h and 4-h groups respectively （P 〈 0. 01 ） ; （2） Erk inhibitor could recover the vascular reac- tivity after 4-h hypoxia, and repress the decreased effect of Ang-2 on vascular reactivity after 4-h hypoxia, and the Emax of NE was increased from 5. 875 to 9. 681 mN and from 3. 444 mN to 9. 003 mN, respectively （P 〈0.01 ） ; （3） At 10 rain after hypoxia, Ang-1 and Tie-2 inhibitors could decrease the phosphorylation of Erk from 0. 6258 to 0. 2643 and 0. 2578 respectively （P 〈 0.01 ）. Conclusion Erk mediated the down- regulation of Ang-2 on the vascular reactivity through its increased phosphorylation in the late period of hemorrhagic shock.

关 键 词：失血性休克 血管反应性 血管生成素 细胞外信号调节激酶 

分 类 号：R605.971[医药卫生—急诊医学]