【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geng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,Bed-erson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表达均高于假手术对照组。与MCAO/R组相比较,MCAO/R+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MCAO/R组比较无显著差异,P>0.05。缺血再灌注22h、46h和70h组,上述5项指标较相应的MCAO/R组均有显著差异,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,以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。更多还原

【Abstract】 AIM:To study the effects of neuregulin-1β (NRG-1β) on the nervous behavioral function,cerebral infarction volume,brain water content (BWC),neuroal apoptosis and aquaporin-4 (AQP-4) expression in astrocytes after cerebral ischemic reperfusion in mice. METHODS:Intraluminal thread methods were applied to establish the middle cerebral artery occlusion reperfusion (MCAO/R) model in mice. Neuregulin-1β (2 μg/kg) was injected into the internal carotid artery for treatment. The nervous behavioral function was evaluated by Bederson’s test. The cerebral infarction volume was observed with tetrazolium chloride (TTC) staining. The BWC was measured by calculating the dry-wet weight ratio. The apoptotic positive cells were counted by immunofluorescence assay. The expression of AQP-4 was determined by immunohistochemical method. RESULTS:Nervous behavioral malfunction appeared in all the mice with left middle cerebral artery occlusion (MCAO) and/or reperfusion. The infarction focus showed in the ischemic hemisphere following the injury. The BWC,the numbers of neuroal apoptotic cells and AQP-4 expression in astrocytes were higher than those in sham control group. In MCAO/R+NRG-1β treatment group,the nervous behavioral function at ischemia 24 h significantly improved,the numbers of apoptotic positive cells reduced and the infarction volume decreased significantly than those in MCAO/R group (P<0.05). The BWC and AQP-4 expression in astrocytes showed no significant difference compared with MCAO/R group (P>0.05). In the reperfusion 22 h,46 h and 70 h groups,the five indexes mentioned above were significantly different from those in the corresponding MCAO/R groups (P<0.05). CONCLUSION:NRG-1β might reduce cerebral edema and infarction volume,and improve the nervous behavioral function via down-regulating the expression of AQP-4 in astrocytes and inhibiting the neuronal apoptosis induced by ischemia reperfusion injury.更多还原