促红细胞生成素对脑缺血的保护作用研究进展

摘要/Abstract

摘要： 体外细胞培养及动物实验证明, 促红细胞生成素对脑缺血损伤具有神经保护和治疗作用。其作用机制可能包括抗谷氨酸兴奋毒性、调节NO 的合成、抗氧化作用、抗炎作用、抗神经元凋亡、促进血管生成、促进神经元再生和神经营养作用等。外源性促红细胞生成素可通过血脑屏障进入脑组织内而发挥神经保护作用, 提示促红细胞生成素有望成为防治脑缺血的一种新药。

关键词: 促红细胞生成素, 脑缺血, 神经保护

Abstract: It has been proved that erythropoietin has neuroprotective effect and therapeutic action on cerebral ischemia in vivo and in vitro. The mechanisms of these actions may be involved in anti-exitotoxicity of aminoglutaric acid, regulating the synthesis of nitric oxide, antioxidation, antiinflammatory, inhibiting neuron apoptosis, accelerating angiogenesis, neurogenesis, neurotrophy and others. In addition, exogenous erythropoietin can enter brain tissue through blood-brain barrier and exert neuroprotection. So it is indicated that erythropoietin can be expected to be a new drug to prevent and treat cerebral ischemia.

Key words: erythropoietin, cerebral ischemia, neuroprotection

中图分类号:

R743. 34

俞月萍, 叶夷露. 促红细胞生成素对脑缺血的保护作用研究进展[J]. 中国临床药理学与治疗学, 2007, 12(6): 609-613.

YU Yue-ping, YE Yi-lu. Recent progress in research of protective effects of erythropoietin on cerebral ischemia[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(6): 609-613.

参考文献

1 Sharples EJ, Thiemermann C, YaqoobMM.Novel applications of recombinant erythropoietin[J]. Curr Opin Pharmacol, 2006;6: 184-189.
2 Zhang F, Signore AP, Zhou Z, et al. Erythropoietin protects CA1 neurons against global cerebral ischemia in rat: potential signaling mechanisms[J]. J Neurosci Res, 2006;83: 1241-1251.
3 Liu R, Suzuki A, Guo Z, et al. Intrinsic and extrinsic erythropoietin enhances neuroprotection against ischemia and reperfusion injury in vitro[J]. J Neurochem, 2006;96: 1101-1110.
4 Eid T, Brines M. Recombinant human erythropoietin for neuroprotection: what is the evidence[J] ? Clin Breast Cancer, 2002; 3: S109-S115.
5 Jacobs K, Shoemaker C, Rudersdorf R, et al. Isolation and characterization of genomic and cDNA clones of human erythropoietin[J]. Nature, 1985;313:806-810.
6 Elliott S, Egrie J, Browne J, et al. Control of rHuEPO biological activity: the role of carbohydrate[J]. Exp Hematol, 2004; 32:1146-1155.
7 Kilic E, Kilic U, Soliz J, et al. Brain-derived erythropoietin protects from focal cerebral ischemia by dual activation of ERK-1/-2 and Akt pathways[J]. Faseb J, 2005; 19:2026-2028.
8 Siren AL, Knerlich F, Poser W, et al. Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain[J]. Acta Neuropathol (Berl), 2001;101:271-276.
9 Juul SE, Stallings SA, Christensen RD.Erythropoietin in the cerebrospinal fluid of neonates who sustained CNS injury[J]. Pediatr Res, 1999; 46:543-547.
10 Juul SE, Harcum J, Li Y, et al. Erythropoietin is present in the cerebrospinal fluid of neonates[J]. J Pediatr, 1997;130: 428-430.
11 Juul SE, Yachnis AT, Rojiani AM, et al. Immunohistochemical localization of erythropoietin and its receptor in the developing human brain[J]. Pediatr Dev Pathol, 1999;2:148-158.
12 Chong ZZ, Kang JQ, Maiese K.Erythropoietin:cytoprotection in vascular and neuronal cells[J]. Curr Drug Targets Cardiovasc Haematol Disord, 2003;3:141-154.
13 Marti HH. Erythropoietin and the hypoxic brain[J]. J Exp Biol, 2004;207: 3233-3242.
14 Bernaudin M, Marti HH, Roussel S, et al. A potential role for erythropoietin in focal permanent cerebral ischemia in mice[J]. J Cereb Blood Flow Metab, 1999; 19:643-651.
15 HeidbrederM, Frohlich F, Johren O, et al. Hypoxia rapidly activates HIF-3alpha mRNA expression[J]. Faseb J, 2003;17: 1541-1543.
16 Prass K, Scharff A, Ruscher K, et al. Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin [J]. Stroke, 2003;34:1981-1986.
17 Aydin A, Genc K, Akhisaroglu M, et al. Erythropoietin exerts neuroprotective effect in neonatal rat model of hypoxic-ischemic brain injury[J]. Brain Dev, 2003;25: 494-498.
18 Li Y, Lu Z, Keogh CL, et al. Erythropoietin-induced neurovascular protection, angiogenesis, and cerebral blood flow restoration after focal ischemia in mice[J]. J Cereb Blood Flow Metab, 2007;27:1043-1054.
19 Kumral A, Ozer E, Yilmaz O, et al. Neuroprotective effect of erythropoietin on hypoxic-ischemic brain injury in neonatal rats [J]. Biol Neonate, 2003;83: 224-228.
20 Yu YP, Xu QQ, Zhang Q, et al. Intranasal recombinant human erythropoietin protects rats against focal cerebral ischemia [J]. Neurosci Lett, 2005; 387:5-10.
21 BrzecK_a A.Brain preconditioning and obstructive sleep apnea syndrome[J]. Acta Neurobiol Exp (Wars), 2005;65:213-220.
22 Juul S. Erythropoietin in the central nervous system, and its use to prevent hypoxic-ischemic brain damage[J]. Acta Paediatr Suppl, 2002;91: 36-42.
23 Kawakami M, Sekiguchi M, Sato K, et al. Erythropoietin receptor-mediated inhibition of exocytotic glutamate release confers neuroprotection during chemical ischemia [J]. J Biol Chem, 2001; 276:39469-39475.
24 Koshimura K, Murakami Y, Sohmiya M, et al. Effects of erythropoietin on neuronal activity[J]. J Neurochem, 1999; 72: 2565-2572.
25 Calapai G, Marciano MC, Corica F, et al. Erythropoietin protects against brain ischemic injury by inhibition of nitric oxide formation[J]. Eur J Pharmacol, 2000; 401:349-356.
26 Genc S, Akhisaroglu M, Kuralay F, et al. Erythropoietin restores glutathione peroxidase activity in 1-methyl-4-phenyL^-1, 2, 5, 6-tetrahydropyridine-induced neurotoxicity in C57BL mice and stimulates murine astroglial glutathione peroxidase production in vitro[J]. Neurosci Lett, 2002;321:73-76.
27 Digicaylioglu M, Lipton SA.Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades[J]. Nature, 2001;412:641-647.
28 Solaroglu I, Solaroglu A, Kaptanoglu E, et al. Erythropoietin prevents ischemia-reperfusion from inducing oxidative damage in fetal rat brain[J]. Childs Nerv Syst, 2003; 19:19-22.
29 Villa P, Bigini P, Mennini T, et al. Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis[J]. J Exp Med, 2003;198:971-975.
30 Vairano M, Dello Russo C, Pozzoli G, et al. Erythropoietin exerts anti-apoptotic effects on rat microglial cells in vitro[J]. Eur J Neurosci, 2002;16: 584-592.
31 Mintzer MZ, Correia CJ, Strain EC.A dose-effect study of repeated administration of buprenorphine/naloxone on performance in opioid-dependent volunteers[J]. Drug Alcohol Depend, 2004;74:205-209.
32 Carmeliet P.Angiogenesis in health and disease[J]. NatMed, 2003;9: 653-660.
33 Buemi M, Caccamo C, Nostro L, et al. Brain and cancer: the protective role of erythropoietin[J]. Med Res Rev, 2005;25: 245-259.
34 Wang L, Zhang Z, Wang Y, et al. Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats[J]. Stroke, 2004;35: 1732-1737.
35 Lichtenwalner RJ, Parent JM.Adult neurogenesis and the ischemic forebrain[J]. J Cereb Blood Flow Metab, 2006; 26:1-20.
36 Lie DC, Song H, Colamarino SA, et al. Neurogenesis in the adult brain:new strategies for central nervous system diseases [J]. Annu Rev Pharmacol Toxicol, 2004; 44:399-421.
37 Tsai PT, Ohab JJ, Kertesz N, et al. A critical role of erythropoietin receptor in neurogenesis and post-stroke recovery[J]. J Neurosci, 2006;26: 1269-1274.
38 Shingo T, Sorokan ST, Shimazaki T, et al. Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells[J]. J Neurosci, 2001; 21:9733-9743.
39 Ferriero DM. Protecting neurons[J]. Epilepsia, 2005;46 Suppl 7:45-51.
40 Tabira T, Konishi Y, Gallyas F Jr. Neurotrophic effect of hematopoietic cytokines on cholinergic and other neurons in vitro[J]. Int J Dev Neurosci, 1995;13: 241-252.

[1]	王金刚, 李强, 孙会艳, 王洪权. 鼠尾草酸在帕金森病中的神经保护作用机制研究进展[J]. 中国临床药理学与治疗学, 2023, 28(9): 1073-1080.
[2]	王坤, 许佩佩, 周兰兰, 鲁晟. 人参皂苷Rg1调控Epac1/Rap1信号通路对缺血性脑卒中大鼠神经保护作用机制研究[J]. 中国临床药理学与治疗学, 2023, 28(7): 721-727.
[3]	梁美芳, 陈庆状, 杨沛群, 王勇. 基于真实世界的阿托伐他汀仿制药和原研药防治缺血性脑卒中/短暂性脑缺血发作的有效性和安全性比较[J]. 中国临床药理学与治疗学, 2022, 27(7): 785-792.
[4]	杨欢, 石玉红, 冉海凤, 陈怡瑾, 徐晓玉. 促红细胞生成素的生理功能及生成来源[J]. 中国临床药理学与治疗学, 2021, 26(4): 434-443.
[5]	张高娇，王芯芯，周佳，王雷雷，戴勤学. 小窝蛋白Cav-1介导人参皂苷Rb1对小鼠脑缺血再灌注损伤的脑保护作用[J]. 中国临床药理学与治疗学, 2020, 25(3): 265-270.
[6]	刘亚东，卢小伟，刘志刚. 促红细胞生成素对急性脊髓损伤患者血清降钙素基因相关肽的影响[J]. 中国临床药理学与治疗学, 2019, 24(8): 933-937.
[7]	肖世庚，董文彬，叶小弟，陈爱瑛，程敏，缪云萍，郑高利. 自噬在米诺环素保护大鼠脑缺血再灌注损伤中的作用研究[J]. 中国临床药理学与治疗学, 2019, 24(7): 730-736.
[8]	俞陈陈，刘树群，刘建龙，曹红，刘雪娇，蔡茜茜. 姜黄素对高血压病大鼠全脑缺血再灌注时海马神经元损伤及皮质酮、SGK1表达的影响[J]. 中国临床药理学与治疗学, 2019, 24(7): 737-743.
[9]	段晋宁, 向常清, 钱爱红, 李进, 陈修全, 韩永峰, 黄娜, 范丽莉. 珠子参皂苷通过激活 PI3K/Akt通路对小鼠脑缺血再灌注损伤的保护作用研究[J]. 中国临床药理学与治疗学, 2019, 24(7): 750-758.
[10]	刘小艳，田野，刘骥飞，苏刚，张振昶. 姜黄素对脑缺血再灌注损伤的保护作用机制研究进展[J]. 中国临床药理学与治疗学, 2019, 24(11): 1305-1309.
[11]	张睿，李冰洁，李庆林. 酸枣仁皂苷A对脂多糖诱导小胶质细胞活化的影响及神经保护作用[J]. 中国临床药理学与治疗学, 2018, 23(2): 126-131.
[12]	徐慧，张民远，戴勤学. miR-145通过调节SOD活性介导人参皂苷Rb1对脑缺血再灌注损伤大鼠的脑保护作用[J]. 中国临床药理学与治疗学, 2018, 23(11): 1215-1220.
[13]	武彩霞，杜冠华. 匹诺塞林对脑缺血再灌注内质网应激凋亡相关基因mRNA表达的影响[J]. 中国临床药理学与治疗学, 2018, 23(1): 34-40.
[14]	朱洁瑾，吴湧，叶晓莉，叶华进，王刚，费霏，李晴宇. 漆黄素对脑缺血再灌注诱导学习记忆损伤及HPA轴的影响[J]. 中国临床药理学与治疗学, 2017, 22(9): 1002-1007.
[15]	沈忱，李运曼，夏念，徐丹，韩丹，陈仕杰. Treg细胞抑制基质金属蛋白酶-9对类风湿性关节炎伴急性脑缺血损伤的研究进展[J]. 中国临床药理学与治疗学, 2017, 22(7): 831-840.