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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。
OBJECTIVE: To investigate the effects of NRG-1β on neurobehavioral function, brain geng infarction volume, brain water content, neuronal apoptosis and the expression of aquaporin-4 AQP-4) expression and neuroprotective mechanism. Methods: The middle cerebral artery occlusion and reperfusion (MCAO / R) model was established by thread occlusion method. After intervention with NRG-1β (2μg / kg) via internal carotid artery, the neurobehavioral function of the animals was evaluated by Bed- TTC staining was used to observe the volume of cerebral infarction. The water content of brain tissue was measured by wet and dry method. Apoptosis was detected by immunofluorescence staining. The expression of AQP-4 was detected by immunohistochemistry. Results: After cerebral ischemia-reperfusion injury, all the animals showed neurobehavioral dysfunction, ischemic lesions with cerebral infarction, water content in brain tissue, the number of apoptotic nerve cells and the expression of AQP-4 in glial cells were higher than those in sham operation group. Compared with MCAO / R group, the neurobehavioral injury in MCAO / R + NRG-1βgroup was significantly improved after 24h of ischemia, the number of apoptotic nerve cells was significantly decreased, the volume of cerebral infarction was significantly reduced, P <0.05; however, There was no significant difference in water volume and AQP-4 expression between MCAO / R group and P> 0.05. At the 22h, 46h and 70h after ischemia / reperfusion, the above five indexes were significantly different from the corresponding MCAO / R group (P <0.05). CONCLUSION: NRG-1β may improve the neurobehavioral function of the animals through down-regulating the expression of AQP-4 and inhibiting the apoptosis of glial cells induced by cerebral ischemia-reperfusion injury in order to reduce brain edema and infarct volume.