神经调节素-1β对小鼠脑缺血再灌注损伤的干预作用及可能的机制  

THE INTERFERING EFFECT AND PROBABLE MECHANISM OF NEUREGULIN-1β ON CEREBRAL ISCHEMIA REPERFUSION INJURY IN MICE

作　　者：王涛[1] 杜芳[1] 郭云良[1] 秦丽华[2] 栾丽菊[2] 宁丽霞[1] 

机构地区：[1]青岛大学医学院附属医院脑血管病研究所,青岛266003 [2]北京大学医学部解剖学系,北京100083

出　　处：《解剖学报》2008年第1期35-39,共5页Acta Anatomica Sinica

基　　金：山东省自然科学基金资助项目(Y2004C04)

摘　　要：目的研究神经调节素-1β(NRG-1β)对小鼠脑缺血再灌注后神经行为功能,脑梗死体积,脑组织含水量,神经细胞凋亡以及胶质细胞水通道蛋白-4(AQP-4)表达的影响和神经保护的作用机制。方法应用线栓法建立小鼠大脑中动脉闭塞再灌注(MCAO/R)模型,经颈内动脉微量注射NRG-1β(2μg/kg)干预治疗,Bederson法评价动物的神经行为功能;氯化三苯基四氮唑(TTC)染色,观察脑梗死体积;干湿重法测定脑组织含水量;免疫荧光染色检测神经细胞凋亡;免疫组织化学检测AQP-4的表达。结果脑缺血再灌注损伤后,动物均表现神经行为功能障碍,缺血侧出现脑梗塞病灶,脑组织含水量、神经细胞凋亡数量和胶质细胞AQP-4表达均高于假手术组。与对照组相比较,NRG-1β治疗组缺血24h,动物神经行为功能损伤明显改善,凋亡神经细胞数明显减少,脑梗塞体积显著缩小(P<0.05);但脑组织含水量和AQP-4表达与对照组比较无显著性差异(P>0.05)。缺血再灌注22h、46h和70h组,上述5项指标较相应的对照组均有显著性差异(P<0.05)。结论NRG-1β可能通过下调脑缺血再灌注损伤诱导的胶质细胞AQP-4表达和抑制细胞凋亡,减轻脑水肿和缩小梗死体积,从而改善动物的神经行为功能。Objective To study the neuroprotective effects of neuregulin-ll3 （NRG-1β） on the nervous behavioral function, cerebral infarction volume, brain water content （BWC）, neuronal apoptosis and aquaporin-4 （AQP-4） expression in astrocytes after cerebral isehemic reperfusion and the related mechanism in mice. Methods Intraluminal thread methods were applied to establish the middle cerebral artery occlusion reperfusion models in the mice. Neuregulin-1β（2μg/kg） was injected into the internal carotid artery for treatment. The nervous behavioral function was evaluated with Bederson＇ s test. The cerebral infarction volume was observed with tetrazolium chloride staining. The BWC was measured by dry-wet weight comparing. The apoptosis positive cells were counted by immunofluorescence assay. The expression of AQP-4 was determined by immunohistochemical assay. Results Nervous behavioral malfunction appeared in all the mice with left middle cerebral artery occlusion and/or reperfusion. The infarction focus showed in the ischemic hemisphere after the injury. The BWC, the number of neuronal apoptosis cells and AQP-4 expression in astrocytes were higher than those in the sham group. In the NRG-1β treatment group, the nervous behavioral function was improved 24 hours after ischemia, the number of apoptosis positive cells reduced and the infarction volume decreased significantly compared with the control group（ P 〈 0.05）. The BWC and AQP-4 expression in astrocytes showed no significant difference compared with the control group（P〉0.05）. In the groups of reperfusion for 22,46 and 70 hours, the five indexes mentioned above were significantly different from those in the corresponding control groups（ P 〈 0.05）. Conclusion NRG-1β may reduce cerebral edema and infarction volume and improve the nervous behavioral function by down-regulating the expression of AQP-4 in astrocytes and inhibiting the neuronal apoptosis induced by ischemia reperfusion injury.

关 键 词：脑缺血 再灌注损伤 脑水肿 细胞凋亡 神经调节素 免疫组织化学 小鼠 

分 类 号：R338[医药卫生—人体生理学] R364[医药卫生—基础医学]