雌激素对缺血性脑卒中的保护作用及相关机制研究进展
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摘要
缺血性脑卒中严重地影响着人们的健康和生命,目前仍缺乏系统的和全面的特异性治疗方式。雌激素在缺血性脑卒中治疗中发挥着重要作用,神经保护作用主要表现在拮抗兴奋性氨基酸毒性、抗氧化应激、扩张血管等21个方面。雌激素受体对缺血性脑卒中的保护作用主要通过基因调控和非基因调控两方面。以上基本上涵盖了雌激素及其受体发挥脑保护作用的全部方面。此外,对雌激素及其受体保护缺血性脑卒中的作用还存在机制不清、药物间药效影响不明、替代治疗等较多问题。
Ischemic stroke seriously affects people's health and life,and there is still lack of systematic and comprehensive treatment methods. Estrogen plays an important role in the treatment of ischemic stroke,and the nerve protection mainly shows in 21 aspects,such as antagonism of excitatory amino acid toxicity,anti-oxidative stress,expansion of blood vessels and so on. The protective effect of estrogen receptor on ischemic stroke is mainly through gene regulation and non-gene regulation. The above mentioned basically covers all the aspects of the protective effects of estrogen and its receptors on the brain. In addition,there are many problems such as unclear mechanism,unknown influence between different drugs,and alternative therapy on the effect of estrogen and its receptor on protecting ischemic stroke.
Ischemic stroke seriously affects people's health and life,and there is still lack of systematic and comprehensive treatment methods. Estrogen plays an important role in the treatment of ischemic stroke,and the nerve protection mainly shows in 21 aspects,such as antagonism of excitatory amino acid toxicity,anti-oxidative stress,expansion of blood vessels and so on. The protective effect of estrogen receptor on ischemic stroke is mainly through gene regulation and non-gene regulation. The above mentioned basically covers all the aspects of the protective effects of estrogen and its receptors on the brain. In addition,there are many problems such as unclear mechanism,unknown influence between different drugs,and alternative therapy on the effect of estrogen and its receptor on protecting ischemic stroke.
引文
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[3] 2015年“世界卒中日”宣传主题及提纲[J].疾病监测,2015,30(10):879-885.
[4] Feigin VL,Krishnamurthi RV,Parmar P,et al. Update on the global burden of ischemic and hemorrhagic stroke in 1990-2013:The GBD 2013 study[J]. Neuroepidemiology,2015,45(3):161-176.
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[7]任弋,季晖,唐苏苏,等.雌激素在中枢神经系统疾病中的作用研究进展[J].药学进展,2017,41(4):290-296.
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[9] Westberry JM,Prewitt AK,Wilson ME. Epigenetic regulation of the estrogen receptor alpha promoter in the cerebral cortex following ischemia in male and female rats[J]. Neuroscience,2008,152(4):982-989.
[10] Zhang W,Koerner IP,Noppens R,et al. Soluble epoxide hydrolase:A novel therapeutic target in stroke[J]. J Cereb Blood Flow Metab,2007,27(12):1931-1940.
[11] Ritzel RM,Capozzi LA,Mccullough LD. Sex,stroke,and inflammation:The potential for estrogen-mediated immunoprotection in stroke[J]. Horm Behav,2013,63(2):238-253.
[12]杨钧哲,李云.女性脑卒中研究进展[J/CD].中西医结合心血管病电子杂志,2017,5(24):105-107.
[13]张雪姣,季晖,唐苏苏,等.雌激素受体在中枢神经系统疾病中的作用[J].药学研究,2018,37(4):221-225.
[14] Saito K,Cui H. Emerging roles of estrogen-related receptors in the Brain:Potential interactions with estrogen signaling.[J]. Int J Mol Sci,2018,19(4):pii:E1091.
[15] Pietras RJ,Szego CM. Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells[J]. Nature,1977,265(5589):69-72.
[16] Pappas TC,Gametchu B,Watson CS. Membrane estrogen receptors identified by multiple antibody labeling and im-peded-ligand binding[J]. FASEB J,1995,9(5):404-410.
[17] Filardo EJ,Quinn JA,Frackelton AR Jr,et al. Estrogen action via the G protein-coupled receptor,GPR30:Stimulation of adenylyl cyclase and c AMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis[J]. Mol Endocrinol,2002,16(1):70-84.
[18] Revankar CM,Cimino DF,Sklar LA,et al. A transmembrane intracellular estrogen receptor mediates rapid cell signaling[J].Science,2005,307(5715):1625-1630.
[19] Weaver CM,Legette LL. Equol,via dietary sources or intestinal production,may ameliorate estrogen deficiency-induced bone loss[J]. J Nutr,2010,140(7):1377-1379S.
[20] Su J,Liu J,Yan XY,et al. Cytoprotective effect of the UCP2-SIRT3 signaling pathway by decreasing mitochondrial oxidative stress on cerebral ischemia-reperfusion injury[J]. Int J Mol Sci,2017,18(7). pii:E1599.
[21] Butterfield JD Jr,Mc Graw CP. Free radical pathology[J]. Stroke,1978,9(5):443-445.
[22] Kinuta Y,Kikuchi H,Ishikawa M,et al. Lipid peroxidation in focal cerebral ischemia[J]. J Neurosurg,1989,71(3):421-429.
[23] Brann D,Raz L,Wang R,et al. Oestrogen signalling and neuroprotection in cerebral ischaemia[J]. J Neuroendocrinol,2015,24(1):34-47.
[24] Furchgott RF,Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine[J].Nature,1980,288(5789):373-376.
[25] Speyer CL,Rancilio NJ,Mcclintock SD,et al. Regulatory effects of estrogen on acute lung inflammation in mice[J]. Am J Physiol Cell Physiol,2005,288(4):881-890.
[26] Mabuchi T,Kitagawa K,Ohtsuki T,et al. Contribution of microglia/macrophages to expansion of infarction and response of oligodendrocytes after focal cerebral ischemia in rats[J]. Stroke,2000,31(7):1735-1743.
[27] Dinarello CA. Biology of Interleukin-1[J]. FASEB J,1988,2(2):108-115.
[28] Dinarello CA. Biologic basis for interleukin-1 in disease[J].Blood,1996,87(6):2095-2147.
[29] Cheng LP,Kuwahara M,Jacobsson J,et al. Inhibition of myointimal hyperplasia and macrophage infiltration by estradiol in aorta allografts[J]. Transplantation,1991,52(6):967-972.
[30] Khalid R. Contributing factors in multiple sclerosis and the female sex bias[J]. Immunol Lett,2014,162(1 Pt 4):223-232.
[31] Behl C,Skutella T,Lezoualc'h F,et al. Neuroprotection against oxidative stress by estrogens:Structure-activity relationship[J].Mol Pharmacol,1997,51(4):535-541.
[32] Mckay LI,Cidlowski JA. Cross-talk between nuclear factor-kappa B and the steroid hormone receptors:Mechanisms of mutual antagonism[J]. Mol Endocrinol,1998,12(1):45-56.
[33] Soares R,Guo S,Russo J,et al. Role of the estrogen antagonist ICI182,780 in vessel assembly and apoptosis of endothelial cells[J].Ultrastruct Pathol,2003,27(1):33-39.
[34] Hurn PD,Macrae IM. Estrogen as a neuroprotectant in stroke[J].J Cereb Blood Flow Metab,2000,20(4):631-652.
[35] White RE,Darkow DJ,Lang JL. Estrogen relaxes coronary arteries by opening BKCa channels through a c GMP-dependent mechanism[J].Circ Res,1995,77(5):936-942.
[36]高艳萍,郭述真.雌激素对绝经后妇女脑功能影响的研究进展[J].现代妇产科进展,2001,10(1):58-59.
[37]刘兴,虞乐华.雌激素神经保护作用及其机制的研究进展[J].现代医药卫生,2016,32(11):1679-1682.
[38] Hokari M,Kuroda S,Iwasaki Y. Pretreatment with the ciclosporin derivative NIM811 reduces delayed neuronal death in the hippocampus after transient forebrain ischaemia[J]. J Pharm Pharmacol,2010,62(4):485-490.
[39]赵捷,王林平,聂继盛,等.苯并[a]芘对大鼠脑组织中神经细胞凋亡及Bcl-2和Bax基因表达的影响[J].中华劳动卫生职业病杂志,2011,29(11):820-824.
[40] Liu G,Wang T,Wang T,et al. Effects of apoptosis-related proteins caspase-3,Bax and Bcl-2 on cerebral ischemia rats[J]. Biomedical Reports,2013,1(6):861.
[41] Dalafave DS,Prisco G. Inhibition of antiapoptotic Bcl-xL,Bcl-2,and Mcl-1 proteins by small molecule mimetics[J]. Cancer Inform,2010,9:169-177.
[42] Terrano DT,Upreti M,Chambers TC. Cyclin-dependent kinase1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis[J]. Mol Cell Biol,2010,30(3):640-656.
[43]樊永梅,王如蜜,张长杰,等.高频电疗对大鼠脑缺血再灌注损伤后caspase-3和海马神经细胞超微结构的影响[J].中南大学学报(医学版),2017,42(1):21-25.
[44] Sharma K,Mehra RD. Long-term administration of estrogen or tamoxifen to ovariectomized rats affords neuroprotection to hippocampal neurons by modulating the expression of Bcl-2 and Bax[J].Brain Res,2008,1204:1-15.
[45]蒋杞英,王志新.雌激素对大鼠局灶性脑缺血神经细胞caspase-3表达的影响[J].河南大学学报(医学版),2009,28(4):264-266.
[46] Dubal DB,Shughrue PJ,Wilson ME,et al. Estradiol modulates bcl-2 in cerebral ischemia:A potential role for estrogen receptors[J].J Neurosci,1999,19(15):6385-6393.
[47]张燕平,刘其强,白宏英.雌激素对慢性脑缺血大鼠认知功能及突触素的影响[J].中国实用神经疾病杂志,2007,10(1):76-78.
[48] Murphy DD,Cole NB,Greenberger V,et al. Estradiol increases dendritic spine density by reducing GABA neurotransmission in hippocampal neurons[J]. J Neurosci,1998,18(7):2550-2559.
[49] Zhang B,Subramanian S,Dziennis S,et al. Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke[J]. J Immunol,2010,184(8):4087-4094.
[50] Glendenning ML,Lovekamp-Swan T,Schreihofer DA. Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats[J]. Neurosci Lett,2008,445(2):188-192.
[51] S9derstr9m I,Strand M,Ingridsson AC,et al. 17beta-estradiol and enriched environment accelerate cognitive recovery after focal brain ischemia[J]. Eur J Neurosci,2009,29(6):1215-1224.
[52]张攀攀,李刚,宋江华,等.星形胶质细胞与雌激素神经保护作用关系的研究进展[J].神经损伤与功能重建,2018,13(3):146-148.
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