低氧预适应是通过亚致死的低氧处理后,激活体内小分子内源性保护机制,让机体对接下来的更严重或致死性低氧刺激产生耐受/抗性。神经细胞是一种能接收和传导兴奋的细胞,对氧含量的变化十分敏感,其能量代谢随氧气变化较为显著。在低氧环境下,神经细胞的腺嘌呤核苷三磷酸(adenosinetriphosphate,ATP)合成减少可激活AMP激活的蛋白激酶[adenosine5’-monophosphate(AMP)-activated protein kinase,AMPK]和TSC1/TSC2复合体抑制哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)。mTOR的一个复合物mTOR复合体1(mTORC1)的表达对机体的能量代谢产生影响。低氧预适应,通过激活或抑制一些基因表达让神经细胞有效利用氧气,使机体产生低氧耐受。在氧浓度低的生存环境下,通过低氧预适应调节能量变化增加机体存活的可能性。高原、航空航天事业、水下作业以及病理性的低氧时,低氧预适应诱导相关分子变化可防止对氧有大量需求的脑组织发生病变,增加神经细胞的存活时间,减少死亡。
[1] Li SJ, Hafeez A, Noorulla F, et al. Preconditioning in neuroprotection: From hypoxia to ischemia[J].Prog Neurobiol, 2017,157:79-91.
[2] Tan X, Azad S, Ji X. Hypoxic preconditioning protects SH-SY5Y cell against oxidative stress through activation of autophagy[J].Cell Transplant, 2018,27(12):1753-1762.
[3] Sun HS, Xu BF, Chen WL, et al. Neuronal K(ATP) channels mediate hypoxic preconditioning and reduce subsequent neonatal hypoxic-ischemic brain injury[J].Exp Neurol,2015,263:161-171.
[4] Huang L, Zhang L. Neural stem cell therapies and hypoxic-ischemic brain injury[J].Prog Neurobiol, 2019,173:1-17.
[5] Bertrand N, Castro DS, Guillemot F. Proneural genes and the specification of neural cell types[J].Nat Rev Neurosci, 2002 ,3(7):517-530.
[6] Bott CJ, Winckler B.Intermediate filaments in developing neurons: Beyond structure[J].Cytoskeleton (Hoboken), 2020, 77(3-4):110-128.
[7] Jessen KR. Glial cells[J].Int J Biochem Cell Biol, 2004, 36(10):1861-1867.
[8] Clairembault T, Leclair-Visonneau L, Neunlist M,et al. Enteric glial cells: new players in Parkinson's disease?[J].Mov Disord, 2015, 30(4):494-498.
[9] Prinz M, Jung S, Priller J. Microglia biology: one century of evolving concepts[J].Cell,2019 ,179(2):292-311.
[10] Nayak D, Roth TL, McGavern DB. Microglia development and function[J].Annu Rev Immunol,2014, 32:367-402.
[11] Zhang N, Yin Y, Han S, et al. Hypoxic preconditioning induced neuroprotection against cerebral ischemic injuries and its cPKCγ-mediated molecular mechanism[J].Neurochem Int, 2011, 58(6):684-92.
[12] Lu N, Li X, Tan R, et al. HIF-1α/Beclin1-mediated autophagy is involved in neuroprotection induced by hypoxic preconditioning[J].J Mol Neurosci,2018 ,66(2):238-250..
[13] Distler U, Schumann S, Kesseler HG, et al. Proteomic analysis of brain region and sex-specific synaptic protein expression in the adult mouse brain[J].Cells, 2020 ,9(2):313.
[14] Huang L, Wan Y, Dang Z, et al. Hypoxic preconditioning ameliorated neuronal injury after middle cerebral artery occlusion by promoting neurogenesis[J].Brain Behav, 2020 ,10(10):e01804.
[15] Zakharova EI, Storozheva ZI, Proshin AT, et al. Opposite pathways of cholinergic mechanisms of hypoxic preconditioning in the hippocampus: Participation of nicotinic α7 receptors and their association with the baseline level of startle prepulse inhibition[J].Brain Sci, 2020 ,11(1):12.
[16] Hu C, Fan L, Cen P, et al. Energy Metabolism plays a critical role in stem cell maintenance and differentiation[J].Int J Mol Sci, 2016,17(2):253.
[17] Folmes CD, Dzeja PP, Nelson TJ, et al. Metabolic plasticity in stem cell homeostasis and differentiation[J].Cell Stem Cell, 2012 ,11(5):596-606.
[18] Brucklacher RM, Vannucci RC, Vannucci SJ. Hypoxic preconditioning increases brain glycogen and delays energy depletion from hypoxia-ischemia in the immature rat[J].Dev Neurosci, 2002,24(5):411-417.
[19] Wang SD, Fu YY, Han XY, et al. Hyperbaric oxygen preconditioning protects against cerebral ischemia/reperfusion injury by inhibiting mitochondrial apoptosis and energy metabolism disturbance[J].Neurochem Res, 2021 ,46(4):866-877.
[20] Wang XJ, Shen K, Wang J, et al. Hypoxic preconditioning combined with curcumin promotes cell survival and mitochondrial quality of bone marrow mesenchymal stem cells, and accelerates cutaneous wound healing via PGC-1α/SIRT3/HIF-1α signaling[J].Free Radic Biol Med, 2020 ,159:164-176.
[21] Brugarolas J, Lei K, Hurley RL, et al.Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex[J].Genes Dev, 2004 ,18(23):2893-2904.
[22] Zong WX, Rabinowitz JD, White E.Mitochondria and cancer[J].Mol Cell, 2016 ,61(5):667-676.
[23] Rose J, Brian C, Woods J, et al.Mitochondrial dysfunction in glial cells: Implications for neuronal homeostasis and survival[J].Toxicology, 2017,391:109-115.
[24] Rangaraju V, Lewis TL Jr, Hirabayashi Y, et al.Pleiotropic mitochondria: the influence of mitochondria on neuronal development and disease[J].J Neurosci, 2019 ,39(42):8200-8208.
[25] Terraneo L, Samaja M.Comparative response of brain to chronic hypoxia and hyperoxia[J].Int J Mol Sci, 2017,18(9):1914.
[26] Coimbra-Costa D, Alva N, Duran M, et al.Oxidative stress and apoptosis after acute respiratory hypoxia and reoxygenation in rat brain[J].Redox Biol, 2017,12:216-225.
[27] Fan X, Wang H, Zhang L, et al.Neuroprotection of hypoxic/ischemic preconditioning in neonatal brain with hypoxic-ischemic injury[J].Rev Neurosci, 2020 ,ahead-of-print/revneuro-2020-0024/revneuro-2020-0024.xml.doi: 10.1515/revneuro-2020-0024.Online ahead of print
[28] Yan Y, Mukherjee S, Harikumar KG, et al.Structure of an AMPK complex in an inactive, ATP-bound state[J].Science, 2021,373(6553):413-419.
[29] Huang J, Liu W, Doycheva DM, et al.Ghrelin attenuates oxidative stress and neuronal apoptosis via GHSR-1α/AMPK/Sirt1/PGC-1α/UCP2 pathway in a rat model of neonatal HIE[J].Free Radic Biol Med, 2019,141:322-337.