Orexin-A对缺血性脑损伤昏迷大鼠促醒作用的研究  

Study on arousal effect of Orexin-A in rat in coma due to ischemic brain injury

作　　者：贾小兵[1] 李露斯[1] 叶建宁[2] 张旭[3] 

机构地区：[1]第三军医大学第一附属西南医院神经内科,重庆400038 [2]第三军医大学第二附属新桥医院神经内科 [3]第三军医大学第二附属新桥医院麻醉科

出　　处：《中国危重病急救医学》2008年第6期361-364,共4页Chinese Critical Care Medicine

基　　金：全军“十一五”医学科研基金资助项目（06MB237）;重庆市自然科学基金资助项目（CSTC2006BB5091）

摘　　要：目的建立一种新的大鼠缺血性脑损伤昏迷模型，并观察Orexin-A对昏迷大鼠的促醒作用。方法通过改良后的四血管阻塞法[4-VO＋6号（直径0．60mm）针头“针控线拴法”]建立大鼠缺血性脑损伤昏迷模型。大鼠在昏迷后120min经侧脑室注射Orexin-A及其受体拮抗剂（SB-334867），观察各组大鼠昏迷时间和脑电、皮质神经元单位放电频率的变化。结果改良后的4-VO能够明显延长大鼠的昏迷时间，达到6～8h且动物无死亡，与4-VO＋4．5号（直径0．45mm）和7号（直径0．70mm）针头“针控线拴法”在昏迷时间上比较差异有统计学意义（F=344．43，P〈0．01）。高剂量Orexin-A（4nmol／10μl）治疗组大鼠的昏迷时间明显缩短，脑电6波比例减少，前额叶皮质神经元单位放电频率增强，与改良后的4-VO组比较差异均有统计学意义（P〈0．05或P〈0．01）；而低剂量Orexin-A（2nmol／10μl）治疗组变化不明显。结论①改良后的4-VO适合做大鼠缺血性脑损伤昏迷模型。②高剂量的Orexin-A对缺血性脑损伤昏迷大鼠有明显的促醒作用。Objective To reproduce an ischemic brain injury coma model and explore the arousal effect of Orexin-A. Methods An ischemic brain injury coma model was reproduced in rats by partial four-vessel occlusion （4-VO with a needle of 0.60 mm in diameter in the lumen to create stenosis of the internal carotid arteries）. One hundred and twenty minutes after the onset of coma, Orexin-A or its antagonist （SB-334867） was given intraventricularly, and the time of coma and changes in electroencephalogram （ECG） were observed, and the unit discharge of neurons in the prefrontal cortex was recorded. Results Partial occlusion of four internal carotid arteries, reducing the lumens to 0.60 mm, could prolong the time of coma to 6 8 hours with the rats still alive. The duration of coma showed a significant difference compared with that in rats who underwent 0.45 mm or 0.70 mm stenosis of the internal carotid arteries （F= 344.43, P〈0.01）. Intraventricular Orexin-A in a dose of 4 nmol/10 μl could obviously decrease the duration of coma with a decrease in 3 wave and increase in unit discharge rate of neurons in coma rats （P〈0.05 or P〈0.01）, but no significant change was observed when the dose was 2 nmol/10μl. Conclusion （1）Creating stenosis of all four internal carotid arteries is suitable to reproduce ischemic brain injury with coma in rats. （2） Intracerebroventricular injection of Orexin-A （4 nmol） has a potent arousal effect on ischemic brain injury coma in rats.

关 键 词：昏迷 大鼠 模型 OREXIN-A 促醒 

分 类 号：R743[医药卫生—神经病学与精神病学]