神经调节素治疗小鼠脑缺血再灌注损伤的机制(英)

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(2 μg/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22 h、46 h和70 h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。

Therapeutic effect and mechanism of neuregulin on cerebral ischemia reperfusion injury in mice

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.