神经调节素对大鼠脑缺血损伤的预防性治疗作用和机制  

The preventive therapeutic effect mechanism of neuregulin on cerebral ischemic injury in rats

作　　者：李琴[1,2] 张睿[2] 梅元武[1] 郭云良[2] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经内科,湖北武汉430030 [2]青岛大学医学院脑血管病研究所,山东青岛266003

出　　处：《中风与神经疾病杂志》2008年第6期658-662,共5页Journal of Apoplexy and Nervous Diseases

基　　金：山东省自然科学基金资助项目(Y2004C04)

摘　　要：目的探讨神经调节素(Neuregulin-1β,NRG-1β)对大鼠脑缺血损伤的预防性治疗作用和机制。方法Wistar大鼠150只,应用线栓法建立大鼠大脑中动脉闭塞(MCAO)模型,随机分为对照组和治疗组,在MCAO前经颈内动脉注射NRG-1β(2μg/kg)进行预防性治疗。在MCAO后0h、0.5h、1.0h、1.5h和2.0h分别用干湿重法测定脑组织含水量,氯化三苯基四氮唑(TTC)染色测定脑梗死体积,免疫荧光法和免疫组化检测脑组织细胞凋亡和早期生长反应基因-1(Egr-1)表达水平。结果大脑中动脉阻断后,动物脑组织含水量和梗死面积随着缺血时间的延长而逐渐增加,NRG-1β预处理组脑组织含水量低于对照组,梗死范围也明显缩小。脑缺血可诱导脑组织细胞凋亡和Egr-1表达,随着缺血时间的延长,凋亡细胞和Egr-1阳性细胞数明显增多;NRG-1β预处理能明显减少缺血诱导的细胞凋亡数,增加Egr-1的表达水平。结论NRG-1β可能通过抑制凋亡途径和诱导Egr-1表达水平,对缺血性脑损伤具有积极的保护作用。Objective To evaluate the preventive therapeutic effects of neuregulin-1 β（NRG-1β） on ischemic cerebral insult in rats. Methods Total of 150 healthy Wistar rats were subjected to establish middle cerebral artery occlusion （MCAO） model by intraluminal thread, and randomly divided into the control group and the pretreatment group. The rats in the pretreatment group were administered NRG-1β（2μg/kg） into internal carotid artery before MCAO. At intervals 0h,0.5 h, 1h, 1.5h and 2h after MCAO operation, the brain water content was measured by dry-wet weight compare, and the cerebral infarction volume with tetrazolium chloride （TTC） stain. The apoptosis and early growth response gene-1 （Egr-1） were determined by immunochemical and immumofluorescent assay. Results After MCAO, the brain water content and the cerebral infarction volume increased successfully according to the ischemic time. NRG-1β pretreatment could decrease the two parameters compared with the control group at the same timepoint. Simultaneously, the cerebral ischemia could induce apoptosis and expressions of Egr-1 in brain tissue. Accompanying by the ischemic time prolong, the number of apoptotie cells and Egr-1 positive cells was increased gradually. NRG-1β pretreatment could decrease obviously the amount of apoptotic cells and increase the expression level of Egr-1 protein. Conclusion NRG-1β might play a cruial neuroprotective effect on ischemic cerebral insult through inhibiting apoptosis and activating some early gene expression.

关 键 词：缺血性脑损伤 脑水肿 神经调节素 细胞凋亡 及早基因 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]