CAJ | 학술논문

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.
목적:연구신경조절소-1β(NRG-1β)대소서뇌결혈재관주후신경행위공능、뇌geng경사체적、뇌조직함수량、신경세포조망이급효질세포수통도단백-4(AQP-4)표체적영향화신경보호작용궤제. 방법:응용선전법건립소서대뇌중동맥폐새재관주(MCAO/R)모형,경경내동맥미량주사NRG-1β(2 μg/kg) 간예치료,Bederson법평개동물적신경행위공능,록화삼분기사담서(TTC)염색관찰뇌경사체적,간습중법측정뇌조직함수량,면역형광염색검측신경세포조망,면역조직화학검측AQP-4적표체.결과:뇌결혈재관주손상후,동물균표현신경행위공능장애,결혈측출현뇌경새병조,뇌조직함수량、신경세포조망수량화효질세포AQP-4표체균고우가수술대조조.여MCAO/R조상비교,MCAO/R+NRG-1β치료조결혈24h동물신경행위공능손상명현개선、조망신경세포수명현감소、뇌경새체적현저축소,P<0.05;단뇌조직함수량화AQP-4표체여MCAO/R조비교무현저차이,P>0.05.결혈재관주22 h、46 h화70 h조,상술5항지표교상응적MCAO/R조균유현저차이,P<0.05.결론:NRG-1β가능통과하조뇌결혈재관주손상유도적효질세포AQP-4표체화억제세포조망,이감경뇌수종화축소경사체적,종이개선동물적신경행위공능.
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.