6-姜酚改善新生小鼠缺氧、缺血性脑损伤后认知行为及其机制

doi:10.16098/j.issn.0529-1356.2023.03.007

摘要/Abstract

摘要：

目的探讨6-姜酚对新生鼠缺氧、缺血性脑损伤（HIE）后认知行为的作用，通过观察对突触可塑性、神经元存活、神经干细胞增殖的影响，探讨6-姜酚对新生小鼠HIE脑损伤保护的作用机制。方法利用出生后第7天昆明小鼠幼仔（78只）进行右侧颈总动脉结扎，然后进行90 min的缺氧处理，构建新生小鼠、缺氧缺血性脑病模型，并通过腹腔注射6-姜酚，利用水迷宫行为学方法检测认知行为；采用2，3，5-三苯基氟化四氮唑（TTC）染色观察脑损伤变化情况；利用透射电子显微镜检测突触结构和数目的改变；采用HE染色、尼氏染色、二氢乙锭（DHE）染色观察各组小鼠脑海马组织病理形态学变化；利用免疫荧光和Real-time PCR检测各组神经干细胞增殖情况和相关转录因子的表达水平；利用Western blotting检测增殖相关信号通路Akt信号通路的变化。结果 6-姜酚早期处理可改善小鼠HIE后成年学习记忆能力，减轻新生小鼠HIE后脑损伤和增加突触数目和结构完整性。6-姜酚处理组HIE病变侧海马细胞排列紊乱现象有所改善，坏死细胞数目减少，海马神经干细胞增殖能力及神经干细胞增殖相关转录因子Nestin和性别决定区转录因子2（Sox2）表达水平显著升高，磷酸化Akt（p-Akt）水平增加。结论 6-姜酚可改善HIE小鼠成年后学习记忆能力并减轻HIE后脑组织损伤，其作用机制可能通过抑制活性氧簇（ROS）的产生而减轻神经元损伤并激活Akt信号通路促进海马神经干细胞的增殖能力。

关键词: 6-姜酚, 缺氧、缺血性脑损伤, 神经干细胞, 神经元, 认知行为, 透射电子显微术, 新生小鼠

Abstract:

Objective To investigate the effect of 6-gingerol treatment on cognitive behavior after hypoxic-ischemic brain injury (HIE) in neonatal mice, and to explore the protective mechanism of 6- gingerol on HIE brain injury in neonatal mice by observing the effects on neuronal survival and neural stem cell proliferation. Methods The right common carotid artery was ligated in Kunming mice（78）on the 7th day after birth and HIE model was established after 90 minutes of hypoxic treatment. 6-gingerol was injected intraperitoneally. The cognitive behavior was detected by Morris water maze test; 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to observe the changes of brain injury; The changes of synaptic structure and number were obseved by transmission electron microscopy; HE staining, Nissl staining and dihydroethidium(DHE) staining were used to observe the pathomorphological changes of hippocampus in each group; The proliferation of neural stem cells and the expression of related transcription factors were detected by immunofluorescence and Real-time PCR; The changes of Akt signal pathway were detected by Western blotting. Results 6-gingerol treatment could improve the long-term learning and memory ability, reduce the brain injury and brain edema of neonatal mice after HIE, and improve synaptic plasticity of mice after HIE. In the 6-gingerol treatment group, the disorder of hippocampal cells in the diseased side of HIE was improved, the number of necrotic cells decreased, the proliferation ability of hippocampal neural stem cells and the expression levels of nestin and sex determining region box transcription factor 2(Sox2) related transcription factors increased significantly, and the level of phosphorylated Akt(p-Akt) increased. Conclusion It is found that 6-gingerol can improve the learning and memory ability of HIE mice in adulthood and reduce brain tissue injury after HIE. 6-gingerol may play a role in inhibiting the production of reactive oxygen species(ROS), reducing neuronal injury and upregulating the expression of Akt signal pathway, promoting the proliferation of hippocampal neural stem cells, so as to provide potential drugs for the treatment of neonatal HIE.

Key words:

6-gingerol, Hypoxic-ischemic brain injury, Neural stem cell, Neuron, Cognitive behavior, Transmission electron microscopy, Neonatal mouse

中图分类号:

R321

姚远赵曼杜静怡周文娟. 6-姜酚改善新生小鼠缺氧、缺血性脑损伤后认知行为及其机制[J]. 解剖学报, 2023, 54(3): 296-304.

YAO Yuan ZHAO Man DU Jing-yi ZHOU Wen-juan. Effect and mechanism of 6-gingerol on neonatal hypoxic-ischemic encephalopathy and cognitive behavior in neonatal mice[J]. Acta Anatomica Sinica, 2023, 54(3): 296-304.

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