孕酮对发育期脑损伤的神经保护作用研究进展
摘要
<正>发育期的大脑,具有一些独特的特征,对内外环境的变化异常敏感,该阶段应用药物干预,效果显著[1]。与成熟大脑相比,未成熟大脑抗氧化能力显著降低[2],小胶质细胞增生较活跃[3-4]。而小胶质细胞与炎症反应密切相关,早期抗炎具有脑区特异性神经保护作用。发育的早期,脑内促凋亡蛋白以较高水平表达,容易启动神经细胞程序性死亡级联反应[5]。此时若增加抗凋亡药物,将减少神经细胞的凋亡,发挥更强的神经保护作用。而目前的许多研究表明孕酮(又称黄体酮)在
引文
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[29] Li X,Han H,Hou R,et al.Progesterone treatment before experimental hypoxia-ischemia enhances the expression of glucose transporter proteins GLUT1 and GLUT3 in neonatal rats[J].Neurosci Bull,2013,29(3):287-294
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[2] Herringa RJ.Trauma,PTSD,and the developing brain[J].Curr Psychiatry Rep,2017,19(10):69
[3] Sominsky L,De Luca S,Spencer SJ.Microglia:key players in neurodevelopment and neuronal plasticity[J].Int J Biochem Cell Biol,2018,94:56-60
[4] Kierdorf K,Erny D,Goldmann T,et al.Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways[J].Nature Neuroscience,2013,16(3):273-280
[5] Liao Z,Cao D,Han X,et al.Both JNK and P38 MAPK pathways participate in the protection by dexmedetomidine against isoflurane-induced neuroapoptosis in the hippocampus of neonatal rats[J].Brain Res Bull,2014,107:69-78
[6] Wei J,Xiao GM.Theneuroprotective effects of progesterone on traumatic brain injury:current status and future prospects[J].Acta Pharmacol Sin,2013,34(12):1485-1490
[7] Liu M,Kelley MH,Herson PS,et al.Neuroprotection of sex steroids[J].Minerva Endocrinol,2010,35(2):127-143
[8] Aryshanian éB.Neuropharmacology of progesterone[J].Eksp Klin Farmako,2014,77(7):39-44
[9] Baulieu EE,Robel P,Schumacher M.Neurosteroids:beginning of thestory[J].Int Rev Neurobiol,2001,46:1-32
[10] Zielniok K,Motyl T,Gajewska M.Functionalinteractions between 17β-estradiol and progesterone regulate autophagy during aciniformation by bovine mammary epithelial cells in 3D cultures[J].Biomed Res Int,2014:382653
[11] Wagner CK.Progesterone receptors and neural development:agapbetween bench and bedside?[J].Endocrinology,2008,149(6):2743-2749
[12] Quadros PS,Wagner CK.Regulation of progesterone receptorexpression by estradiol is dependent on age,sex and region in the ratbrain[J].Endocrinology,2008,149(6):3054-3061
[13] Meffre D,Labombarda F,Delespierre B,et al.Distribution of membrane progesterone receptor alpha in the male mouse and rat brain and its regulation after traumatic brain injury[J].Neuroscience,2013,231:111-124
[14] Kierdorf K,Erny D,Goldmann T,et al.Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways[J].Nat Neurosci,2013,16(3):273-280
[15] Brunton PJ,Russell JA,Hirst JJ.Allopregnanolone in the brain:Protecting pregnancy and birth outcomes[J].Prog Neurobiol,2014,113:106-136
[16] Zhu X,Fréchou M,Liere P,et al.A role of endogenous progesterone in stroke cerebroprotection revealed by the neural-specific deletion of its intracellular receptors[J].J Neurosci,2017,37(45):10998-11020
[17] Peterson BL,Won S,Geddes RI,et al.Sex-related differences in effects of progesterone following neonatal hypoxic brain injury[J].Behav Brain Res,2015,286:152-165
[18] Hirst JJ,Palliser HK,Shaw JC,et al.Birth and neonatal transition in the guinea pig:experimental approaches toprevent preterm birth and protect the premature fetus[J].Front Physiol,2018,9:1802
[19] Tsuji M,Taguchi A,Ohshima M,et al.Progesterone and allopregnanolone exacerbate hypoxic-ischemic brain injury in immature rats[J].Exp Neurol,2012,233(1):214-220
[20] Hirst JJ,Kelleher MA,Walker DW,et al.Neuroactive steroids in pregnancy:key regulatory and protective roles in the foetalbrain[J].J Steroid Biochemistry Mol Biol,2014,139:144-153
[21] Fabres RB,daRosa LA,de Souza SK,et al.Effects of progesterone on the neonatal brain following hypoxia-ischemia[J].Metab Brain Dis,2018,33(3):813-821
[22] Gaignard P,Liere P,Thérond P,et al.Role of sex hormones on brain mitochondrial function,with special reference to aging and neurodegenerative diseases[J].Front Aging Neurosci,2017,9:406
[23] Wang X,Zhang J,Yang Y,et al.Progesterone attenuates cerebral edema in neonatal rats with hypoxic-ischemic brain damage by inhibiting the expression of matrix metalloproteinase-9 and aquaporin-4[J].Exp Ther Med,2013,6(1):263-267
[24] Ferrazzano P,Chanana V,Uluc K,et al.Age-dependent microglial activation in immature brains after hypoxia-ischemia[J].CNS Neurol Disord Drug Targets,2013,12(3):338-349
[25] Wang X,Zhang J,Si D,et al.Progesterone inhibits the expression of cycloxygenase-2 and interleukin-1β in neonatal rats with hypoxic ischemic brain damage[J].Int J Neurosci,2014,124(1):42-48
[26] Novak CM,Ozen M,Mclane M,et al.Progesterone improves perinatal neuromotor outcomes in a mouse model of intrauterine inflammation via immunomodulation of the placenta[J].Am J Reprod Immunol,2018,79(5):e12842
[27] Sun F,Nguyen T,Jin X,et al.Pgrmc1/BDNF signaling plays a critical role in mediating glia-neuron cross talk[J].Endocrinology,2016,157(5):2067-2079
[28] Atif F,Yousuf S,Stein DG.Progesterone in the treatment of neonatal arterial ischemic stroke and acute seizures:role of BDNF/TrkB signaling[J].Neuropharmacology,2016,107:317-328
[29] Li X,Han H,Hou R,et al.Progesterone treatment before experimental hypoxia-ischemia enhances the expression of glucose transporter proteins GLUT1 and GLUT3 in neonatal rats[J].Neurosci Bull,2013,29(3):287-294
[30] Wessel L,Balakrishnan-Renuka A,Henkel C,et al.Long-term incubation with mifepristone (MLTI) increases the spine density in developing Purkinje cells:new insights into progesterone receptor mechanisms[J].Cell Mol Life Sci,2014,71(9):1723-1740
[31] Kasubuchi M,Watanabe K,Hirano K,et al.Membrane progesterone receptor beta (mPRβ/Paqr8) promotes progesterone-dependent neurite outgrowth in PC12 neuronal cells via non-G protein-coupled receptor (GPCR) signaling[J].Sci Rep,2017,7:5168