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已有研究表明乙酰胆碱酯酶抑制剂多奈哌齐和加兰他敏具有减轻氧糖剥夺导致的神经元损伤并减小脑缺血动物的脑梗死体积的作用,但它们的这种作用可能并不完全依赖于其胆碱酯酶抑制活性。为了进一步研究多奈哌齐和加兰他敏对脑缺血后神经元损伤的作用,本课题组成功建立了体外大鼠神经元-星形胶质细胞共培养模型,并在该共培养模型的基础上研究多奈哌齐和加兰他敏对氧糖剥夺/复氧(oxygen-glucose deprivation/reoxygenation,OGD/R)后神经元凋亡的作用及其可能的作用机制。结果表明,多奈哌齐和加兰他敏可以明显减轻OGD/R后共培养体系中的神经元凋亡,同时,促进共培养体系中星形胶质细胞合成和分泌BDNF和NGF,并激活星形胶质细胞内的PI3K/Akt通路和ERK通路,促进核转录因子CREB的磷酸化。以上结果说明多奈哌齐和加兰他敏对OGD/R导致的神经元损伤具有保护作用,其机制可能与激活星形胶质细胞内的PI3K/Akt通路和ERK通路,促进核转录因子CREB的磷酸化,进而促进星形胶质细胞合成和分泌BDNF和NGF有关。
It has been reported that donepezil and galantamine, an acetylcholinesterase inhibitor, have the effect of reducing neuronal damage caused by oxygen deprivation and decreasing cerebral infarction volume in cerebral ischemic animals, but their effects may not be completely dependent In its cholinesterase inhibitory activity. In order to further study the effect of donepezil and galantamine on neuronal damage after cerebral ischemia, our group established a successful in vitro rat neuronal-astrocyte co-culture model, and on the basis of the co-culture model To investigate the effects of donepezil and galantamine on neuronal apoptosis after oxygen glucose deprivation / reoxygenation (OGD / R) and its possible mechanism. The results showed that donepezil and galantamine can obviously reduce the apoptosis of neurons in co-culture system after OGD / R, promote the synthesis and secretion of BDNF and NGF in astrocytes in coculture system, and activate starches The PI3K / Akt pathway and the ERK pathway in the stromal cells promote the phosphorylation of the nuclear transcription factor CREB. These results suggest that donepezil and galantamine have a protective effect on OGD / R-induced neuronal injury possibly through activating the PI3K / Akt pathway and ERK pathway in astrocytes and promoting the phosphorylation of nuclear transcription factor CREB , And then promote astrocyte synthesis and secretion of BDNF and NGF.