尾加压素Ⅱ、丝裂原活化蛋白激酶在预缺血联合巴曲酶处理缺血性大鼠脑损伤中的表达  

Urotensin Ⅱ and Mitogen-activated Protein Kinase Expression of Batroxobin and Ischemic Preconditioning on Ischemic Rats Cerebral Injury

作　　者：徐佳亮[1] 姜美子[2] 何志义[1] 李蕾[1] 

机构地区：[1]中国医科大学第一临床医院神经内科,辽宁沈阳110001 [2]延边大学附属医院神经内科,吉林延吉133000

出　　处：《中国神经免疫学和神经病学杂志》2009年第1期25-29,共5页Chinese Journal of Neuroimmunology and Neurology

摘　　要：目的探讨尾加压素Ⅱ(UⅡ)和丝裂原活化蛋白激酶(MAPK)信号转导通路在缺血性脑损伤中的病理生理作用及巴曲酶增强缺血耐受现象的脑保护作用。方法采用预缺血大鼠局灶性脑缺血模型,将大鼠随机分为假手术组、缺血性损伤组、预缺血组、预缺血联合巴曲酶组4组,各组按大脑中动脉永久性阻断后3、6、24、72 h再分为4个亚组。应用免疫组织化学法检测各亚组UⅡ及孤儿G蛋白耦联受体14(GPR14)免疫活性,Westernblot法检测各亚组MAPK亚型ERK和JNK表达。结果各组大鼠大脑中动脉永久性阻断后24 h其大脑UⅡ和GPR14阳性细胞表达达高峰;同一时间点间比较,预缺血联合巴曲酶组可明显改善大鼠脑损伤症状,明显降低UⅡ和GPR14表达,增强磷酸化ERK表达,减弱磷酸化JNK表达。结论巴曲酶可通过抑制UⅡ的合成降低其促血管平滑肌增殖和血管收缩效应,以及促进ERK生存通路和抑制JNK死亡通路而增强内源性脑保护作用。Objective To investigate the pathophysiologic effects of Urotensin Ⅱ （U Ⅱ） and mitogen-activated protein kinase （MAPK） signal conducting pathway on ischemic cerebral injury, and batroxobin improving ischemic tolerance and cerebral protection. Methods We made ischemic preconditioning focal ischemia model, and adopted immunohistochemical method to determine each subgroup UⅡ and orphan G-protein-coupled receptor （GPR14） activities, and western blot method to determine subgroup ERK and JNK activities expression. We divided the rats into four groups： sham group, ischemic injury group, isehemic preconditioning group, ischemic preconditioning＋ batroxobin group and each group was divided into four subgroups at permanent middle cerebral artery occlusion （MCAO） 3 h, 6 h, 24 h, 72 h. Results At permanent MCAO 24 h, each group U Ⅱ, GPR14 positive cells expression reached peak; at the same time point batroxobin＋ischemic preconditioning could improve notably the neurologic deficient symptoms in rats; at every observed time end-point, batroxobin ＋ ischemic preconditioning could attenuate obviously the U Ⅱ, GPR14 exression, enhance the phosphorylation of ERK expression, and down regulate the phosphorylation of JNK expression. Conclusions Batroxobin could inhibit UⅡ synthesis as to decrease the vaso-constriction effect, improve ERK survival way, and inhibit JNK death way to enhance the cerebral ischemie tolerance and cerebral protection.

关 键 词：尾加压素Ⅱ 丝裂原活化蛋白激酶 预缺血 缺血性损伤 巴曲酶 

分 类 号：R743[医药卫生—神经病学与精神病学]