kappa阿片受体激动剂对轻度颅脑爆震伤小鼠认知功能的保护作用及其可能机制  

kappa opioid receptor agonist protects cognitive function in mice with mild craniocerebral blast injury and its possible mechanism

作　　者：高蕾[1] 戴晶 刘颖[1] 柳云恩[1] 金红旭[1] Gao Lei;Dai Jing;Liu Ying;Liu Yun-en;Jin Hong-xu(Department of Emergency Medicine,General Hospital of Shen-Yang Military Region,Shenyang 110840,China)

机构地区：[1]原中国人民解放军沈阳军区总医院急诊医学部,辽宁沈阳110840

出　　处：《中国急救医学》2018年第8期672-675,共4页Chinese Journal of Critical Care Medicine

基　　金：辽宁省自然科学基金项目（201602771）

摘　　要：目的 探讨轻度爆震伤后小鼠认知功能的改变，及kappa阿片受体特异性激动剂U50488对其保护作用及可能机制。方法 雄性昆明小鼠，随机分为空白组（S组）、爆震伤模型组（b-TBI组）和U50488干预组（b-TBI＋U50488组），每组20只，各组再分为伤后1 d、3 d、7 d及水迷宫组四个亚组，每组5只。采用自制爆震伤自动发生装置制作轻度颅脑爆震伤小鼠模型，U50488干预组小鼠造模前15 min给予U50488（10 mg/kg）腹腔注射。空白组及b-TBI组小鼠造模前15 min仅给予等量生理盐水。采用免疫印迹法（Western blot）检测各组小鼠脑组织高迁移率蛋白家族（HMGB-1）、白细胞介素-1（IL-1）、胆碱能抗炎通路相关蛋白α7nAChR表达变化。应用水迷宫逃避潜伏期长短及mNSS评分评估其认知功能。 结果 与空白对照组比较，b-TBI组小鼠mNSS评分更高，水迷宫逃避潜伏期更长（P〈0.05），中枢神经系统IL-1、HMGB-1表达明显升高（P〈0.05）。与b-TBI组比较，U50488干预组小鼠mNSS评分明显下降，水迷宫逃避潜伏期明显减小（P〈0.05），IL-1、HMGB-1表达降低，而胆碱能抗炎通路相关蛋白α7nAChR表达增加（P〈0.05）。结论 ①轻度颅脑爆震伤可以导致认知功能障碍，并与脑组织炎症反应的发生密切相关。②kappa阿片受体的激活可以对爆震伤后小鼠的认知功能起到保护作用，其作用机制可能与激活胆碱能抗炎通路及减轻中枢神经系统炎症反应相关。Objective To investigate the changes of cognitive function in mice after mild blast injury and the protective effect of kappa opioid receptor specific agonist U50488 on it and its possible mechanism. Methods The male Kunming mice were randomly divided into control group （group S） , blast injury model group （group b-TBI） , and U50488 intervention group （b- TBI ＋ U50488 group）, 20 rats in each group; each group was further divided into 1 d, 3 d, 7 d, and water maze group, four subgroups after injury, 5 rats in each group. The homemade explosive injury automatic device was used to make explosive injury model in mice. The mice in KORS group were given US0488U 10 mg/kg of U50488 15 rain before the shock. The mice in the sham group and b - TBI group were given only the same amount of normal saline before injury. Western blot was used to detect the high mobility protein family （ HMGB - 1 ）, interleukin - 1 （ IL - 1 ） and cholinergic anti - inflammatory pathway protein in the brain tissue of mice in each group. The cognitive function was evaluated by using water maze escape latency and mNSS score. Results Compared with the blank control group, the mNSS score of the mice in the b - TBI group was higher than that in the control group ; Water maze escape assay showed that the latency was longer （ P 〈 O. 05 ） ; and the expression of IL - 1 and HMGB - 1 in central nervous system increased significantly （P 〈 0.05 ）. Compared with b - TBI group, the mNSS score of mice in U50488 intervention group decreased significantly, and the escape latency of water labyrinth decreased significantly （ P 〈 0.05 ）, but the expression of ot7nAChR associated with cholinergic anti - inflammatory pathway was increased （P 〈 0. 05 ）. Conclusion Mild blast brain injury can lead to cognitive dysfunction, and is closely related to the occurrence of brain inflammation. The activation of Kappa opioid receptor can protect the cognitive function of mice after blast injury. The mechanism of action may be related

关 键 词：胆碱能抗炎通路 爆震伤 脑损伤 认知障碍 

分 类 号：R971.1[医药卫生—药品]