基于BCL-XL/Bax/Caspase-3/p53/CREB/BDNF信号通路解析南极磷虾蛋白肽辅助增强记忆的靶向作用机理  

Analysis of Targeting Mechanism of Memory Enhancing Peptides Assisted by Antarctic Krill Based on the BCL-XL/Bax/Caspase-3/p53/CREB/BDNF Signaling Pathway

作　　者：郑景如 孙娜[1,2] 杨晶琦 林松毅 Zheng Jingru;Sun Na;Yang Jingqi;Lin Songyi(National Engineering Research Center of Seafood,School of Food Science and Technology,Dalian Polytechnic University,Dalian 116034,Liaoning;Engineering Research Center of Special Dietary Food of Liaoning Province,Food Engineering Technology Research Center of Liaoning Province,Dalian 116034,Liaoning)

机构地区：[1]大连工业大学食品学院、国家海洋食品工程技术研究中心,辽宁大连116034 [2]辽宁省特殊膳食食品工程技术研究中心、辽宁省食品工程技术研究中心,辽宁大连116034

出　　处：《中国食品学报》2024年第8期206-215,共10页Journal of Chinese Institute Of Food Science and Technology

基　　金：国家自然科学基金项目(32022067);辽宁省“兴辽英才计划”青年拔尖人才项目(XLYC2007078)。

摘　　要：目的:探索南极磷虾蛋白肽(EHAK)对东莨菪碱所致小鼠记忆损伤的预防作用。方法:将小鼠分为5组:空白对照组、记忆损伤模型组、南极磷虾蛋白肽低(31.25 mg/kg)、中(62.5 mg/kg)、高(125 mg/kg)剂量组,测定小鼠行为学指标、血清以及海马的生化指标和神经细胞蛋白表达水平,观察海马神经元状态。结果:行为实验表明EHAK能提高小鼠的空间学习记忆能力。在氧化应激水平和胆碱能系统方面,与模型组相比,125 mg/kg EHAK组小鼠血清中超氧化物歧化酶(SOD)活性升高(10.13±1.00)U/mg prot,丙二醛(MDA)含量降低(1.04±0.26)nmol/mg prot,乙酰胆碱(ACh)含量增加(10.13±1.00)μg/mg prot,乙酰胆碱酯酶(AChE)活性和MDA含量分别下降(0.90±0.05)U/mg prot和(1.16±0.01)nmol/mg prot。这些数据表明,EHAK通过预防氧化应激和胆碱能功能障碍来减轻东莨菪碱诱导的认知障碍。海马神经元状态显示南极磷虾蛋白肽可有效预防海马神经元凋亡,发生排列不均等情况。此外,EHAK可通过BCL-XL/Bax/Caspase-3/p53/CREB/BDNF信号通路抑制神经元凋亡,调节神经元的可塑性。结论:EHAK通过调节胆碱能系统和保护海马神经元来预防东莨菪碱引起的记忆障碍,提示EHAK有潜力作为有关功能食品的组成成分。The study aimed to explore the preventive effect of Antarctic krill protein peptide(EHAK)on memory injury caused by scopolamine in mice.The mice were divided into 5 groups:Blank control group,memory damage model group,and low(31.25 mg/kg),medium(62.5 mg/kg)and high(125 mg/kg)dose groups of EHAK.The behavioral indices,serum and biochemical indices of the mice and the protein expression levels of hippocampal nerve cells were determined,and the states of hippocampal neurons were observed.Behavioral experiments indicated that EHAK could improve the spatial learning and memory ability of mice.Regarding the oxidative stress levels and cholinergic systems,when 125 mg/kg EHAK was administered to mice,compared with the model group,the SOD activity in serum increased by(10.13±1.00)U/mg prot and the MDA content in serum decreased by(1.04±0.26)nmol/mg prot.The hippocampal AChE activity and MDA content declined by(0.90±0.05)U/mg prot and(1.16±0.01)nmol/mg prot,respectively,while the ACh content increased by(10.13±1.00)μg/mg prot.These data indicated that EHAK could attenuate scopolamine-induced cognitive impairment by preventing oxidative stress and cholinergic dysfunction.The status of hippocampal neurons showed that the EHAK could effectively prevent hippocampal neuron apoptosis and uneven arrangement.In addition,EHAK could inhibit neuronal apoptosis and regulate prominent plasticity through the BCL-XL/Bax/Caspase-3/p53/CREB/BDNF signaling pathway.Therefore,EHAK could prevent scopolamine-induced memory impairment by modulating the cholinergic system and protecting neurons in the hippocampus,which demonstrated the potential to be used as food ingredient with functional appeal.

关 键 词：南极磷虾蛋白肽 记忆损伤 信号通路 

分 类 号：TS254.1[轻工技术与工程—水产品加工及贮藏工程]