各种原因引起的睡眠时间减少已成为生活常态,睡眠剥夺会降低机体的学习记忆能力,影响生活质量。该研究对C57BL/6J小鼠进行21 d睡眠剥夺,同时每天对小鼠灌胃壳三糖(chitotriose, COS3)和壳五糖(chitopentaose, COS5),通过体重、新物体识别实验、病理学染色、氧化应激和凋亡相关蛋白表达评估COS3和COS5的保护作用。结果显示,COS3和COS5干预能够缓解小鼠体重下降和海马神经细胞坏死变形,显著提高海马组织中超氧化物歧化酶水平和总抗氧化能力,显著降低海马丙二醛含量。COS3和COS5干预能够显著提升海马p-PI3K(phospho-phosphotylinosital 3 kinase)和p-Akt(phospho-protein kinase B)蛋白的相对表达量,激活PI3K/Akt信号通路,缓解神经细胞凋亡。研究表明,COS3和COS5能够明显改善睡眠剥夺引起的学习记忆能力下降,其机制可能与COS3和COS5能够缓解海马组织氧化应激和神经细胞凋亡有关,其中COS3的效果优于COS5。
Reduced sleep duration triggered by various factors has become a normal part of life.Sleep deprivation reduces the learning and memory capacity of the organism and affects the quality of life.In this study, C57BL/6J mice were subjected to sleep deprivation for 21 days, while chitotriose (COS3) and chitopentaose (COS5) were gavaged daily.The protective effects of COS3 and COS5 were assessed by weight, new object recognition assay, pathological staining, oxidative stress, and expression of the apoptosis-associated protein.Results showed that the intervention of COS3 and COS5 relieved the decrease in weight and necrosis and deformation of hippocampal neuronal cells.Additionally, the intervention of COS3 and COS5 improved the superoxide dismutase and total antioxidant capacity in the hippocampus and relieved malondialdehyde levels in the hippocampus.The intervention of COS3 and COS5 could significantly improve the relative expression of phospho-phosphotylinosital 3 kinase (p-PI3K) and phospho-protein kinase B (p-Akt) in the hippocampus, activate the PI3K/Akt signaling pathway and alleviate neuronal apoptosis.These results indicated that COS3 and COS5 had significant protective effects on the decline in learning memory capacity induced by sleep deprivation, with COS3 demonstrating a more significant effect compared to COS5.The mechanism may be related to the abilities of COS3 and COS5 to alleviate oxidative damage and neuronal apoptosis in the hippocampus of mice.
[1] CHATTU V K, MANZAR M D, KUMARY S, et al.The global problem of insufficient sleep and its serious public health implications[J].Healthcare, 2018, 7(1):7010001.
[2] XUE R, WAN Y H, SUN X Q, et al.Nicotinic mitigation of neuroinflammation and oxidative stress after chronic sleep deprivation[J].Frontiers in Immunology, 2019, 10:2546.
[3] PANGESTUTI R, KIM S K.Marine-derived bioactive materials for neuroprotection[J].Food Science and Biotechnology, 2013, 22(5):1-12.
[4] ZHU L M, LI R L, JIAO S M, et al.Blood-brain barrier permeable chitosan oligosaccharides interfere with β-amyloid aggregation and alleviate β-amyloid protein mediated neurotoxicity and neuroinflammation in a dose- and degree of polymerization-dependent manner[J].Marine Drugs, 2020, 18(10):488.
[5] WANG B, WANG L, QU Y F, et al.Chitosan oligosaccharides exert neuroprotective effects via modulating the PI3K/Akt/Bcl-2 pathway in a Parkinsonian model[J].Food & Function, 2022, 13(10):5838-5853.
[6] DAI X L, HOU W Q, SUN Y X, et al.Chitosan oligosaccharides inhibit/disaggregate fibrils and attenuate amyloid β-mediated neurotoxicity[J].International Journal of Molecular Sciences, 2015, 16(5):10526-10536.
[7] ZHANG X X, LIANG S, GAO X H, et al.Protective effect of chitosan oligosaccharide against hydrogen peroxide-mediated oxidative damage and cell apoptosis via activating Nrf2/ARE signaling pathway[J].Neurotoxicity Research, 2021, 39(6):1708-1720.
[8] WU W, WEI W, LU M, et al.Neuroprotective effect of chitosan oligosaccharide on hypoxic-ischemic brain damage in neonatal rats[J].Neurochemical Research, 2017, 42(11):3186-3198.
[9] LI K C, XING R E, LIU S, et al.Separation of chito-oligomers with several degrees of polymerization and study of their antioxidant activity[J].Carbohydrate Polymers, 2012, 88(3):896-903.
[10] 汪玲. 单一聚合度壳寡糖的分离及其对帕金森模型小鼠的神经保护作用研究[D].无锡:江南大学, 2022.
WANG L.Separation of chitosan oligosaccharide monomers with single degree of polymerization and the study of their neuroprotection in parkinsonian mice model[D].Wuxi:Jiangnan University, 2022.
[11] 国家卫生计生委. 关于批准壳寡糖等6种新食品原料的公告(2014年第6号)[J].中国食品添加剂, 2014(4):177-179.
National Health and Family Planning Commission.Announcement on the approval of six new food ingredients, including chitosan (No.6 of 2014)[J].China Food Additives, 2014(4):177-179.
[12] MARTINS P J F, D’ALMEIDA V, NOBREGA J N, et al.A reassessment of the hyperphagia/weight-loss paradox during sleep deprivation[J].Sleep, 2006, 29(9):1233-1238.
[13] LI X, LIU Q Q, YU J Y, et al.Costunolide ameliorates intestinal dysfunction and depressive behaviour in mice with stress-induced irritable bowel syndrome via colonic mast cell activation and central 5-hydroxytryptamine metabolism[J].Food & Function, 2021, 12(9):4142-4151.
[14] XU Z Q, GAO C Y, FANG C Q, et al.The mechanism and characterization of learning and memory impairment in sleep-deprived mice[J].Cell Biochemistry and Biophysics, 2010, 58(3):137-140.
[15] LIU P, LI H, XU H Y, et al.Chitooligosaccharides attenuated hepatic encephalopathy in mice through stabilizing gut-liver-brain disturbance[J].Molecular Nutrition & Food Research, 2023, 67(1):e2200158.
[16] GUAN Z W, PENG X W, FANG J D.Sleep deprivation impairs spatial memory and decreases extracellular signal-regulated kinase phosphorylation in the hippocampus[J].Brain Research, 2004, 1018(1):38-47.
[17] JIANG M R, GUO Z M, WANG C P, et al.Neural activity analysis of pure chito-oligomer components separated from a mixture of chitooligosaccharides[J].Neuroscience Letters, 2014, 581:32-36.
[18] SALEHPOUR F, FARAJDOKHT F, ERFANI M, et al.Transcranial near-infrared photobiomodulation attenuates memory impairment and hippocampal oxidative stress in sleep-deprived mice[J].Brain Research, 2018, 1682:36-43.
[19] TSIKAS D.Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples:Analytical and biological challenges[J].Analytical Biochemistry, 2017, 524:13-30.
[20] 陈逸伦. 壳寡糖对新生大鼠酒精性神经损伤的缓解作用研究[D].无锡:江南大学, 2021.
CHEN Y L.Effect of chitooligosaccharide on ethanol-induced nerve injury in neonatal rats[D].Wuxi:Jiangnan University, 2021.
[21] KıSADERE I·, KARAMAN M, AYDıN M F, et al.The protective effects of chitosan oligosaccharide (COS) on cadmium-induced neurotoxicity in Wistar rats[J].Archives of Environmental & Occupational Health, 2022, 77(9):755-763.
[22] 李克成. 单一聚合度和特定N-乙酰化壳寡糖的分离及抗氧化活性研究[D].北京:中国科学院大学, 2013.
LI K C.Study on separation and antioxidant activity of chitosan oligosaccharide with single polymerization degree and specific N-acetylation[D].Beijing:University of Chinese Academy of Sciences, 2013.
[23] LI Z H, CHENG L, WEN C, et al.Activation of CNR1/PI3K/AKT pathway by tanshinone IIA protects hippocampal neurons and ameliorates sleep deprivation-induced cognitive dysfunction in rats[J].Frontiers in Pharmacology, 2022, 13:823732.
[24] CAO Y, LI Q L, LIU L L, et al.Modafinil protects hippocampal neurons by suppressing excessive autophagy and apoptosis in mice with sleep deprivation[J].British Journal of Pharmacology, 2019, 176(9):1282-1297.
[25] WEI Y Z, ZHOU J Y, YU H Y, et al.AKT phosphorylation sites of Ser473 and Thr308 regulate AKT degradation[J].Bioscience, Biotechnology, and Biochemistry, 2019, 83(3):429-435.
[26] XU Y Y, ZHANG Q, YU S, et al.The protective effects of chitooligosaccharides against glucose deprivation-induced cell apoptosis in cultured cortical neurons through activation of PI3K/Akt and MEK/ERK1/2 pathways[J].Brain Research, 2011, 1375:49-58.
[27] 贾鹏. 壳寡糖减缓大鼠髓核细胞退变的实验研究[D].武汉:武汉大学, 2017.
JIA P.Chitosan oligosaccharides protect nucleus pulposus cells from degeneration in A rat experimental model[D].Wuhan:Wuhan University, 2017.
[28] YANG Y, XING R E, LIU S, et al.Immunostimulatory effects of chitooligosaccharides on RAW 264.7 mouse macrophages via regulation of the MAPK and PI3K/akt signaling pathways[J].Marine Drugs, 2019, 17(1):36.
