亚甲蓝对脑缺血再灌注损伤保护机制的研究进展

doi:103969/jissn1002-1949201809019

摘要
图/表
参考文献(49)
相关文章 (2)

全文: PDF (555 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要大脑是人体各器官中对缺血、缺氧最为敏感的器官。各种原因引起的脑部缺血，可造成脑部的缺血性损伤，但在随后的治疗中恢复再灌注后又会引起活性氧的大量产生，通过各种分子机制最终导致神经元细胞的坏死或凋亡引发再灌注损伤。亚甲蓝（MB）作为一种神经系统疾病研究热点药物，具有抗氧化性，可迅速穿过血脑屏障，对脑部神经元细胞有一定保护作用。本文将对脑缺血/再灌注（I/R）损伤机制及亚甲蓝对脑缺血/再灌注损伤的保护机制进行综述。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	苏成洋
	尹路路
	李小燕
	钟春婷
	耿男
	庞燕
	李培杰
	曹雯

关键词 ：脑缺血/再灌注（I/R）损伤, 亚甲蓝（MB）, 活性氧（ROS）

通讯作者: 李培杰（1962-），男，教授，研究生导师，科主任，E-mail：lipeijielanzhou@hotmail.com。

作者简介: 苏成洋（1989-），男，硕士，住院医师，E-mail：834322172@qq.com。

引用本文:

苏成洋，尹路路，李小燕，钟春婷，耿男，庞燕，李培杰，曹雯. 亚甲蓝对脑缺血再灌注损伤保护机制的研究进展[J]. 中国急救医学, 2018, 38(9): 827-832.
Su Cheng-yang, Yin Lu-lu, Li Xiao-yan, Zhong Chun-ting, Geng Nan, Pang Yan, Li Pei-jie, Cao Wen. Research progress on the protective mechanism of methylene blue against cerebral ischemia and reperfusion injury. Chinese Journal of Critical Care Medicine, 2018, 38(9): 827-832.

链接本文:

http://www.cnemergency.org.cn/CN/103969/jissn1002-1949201809019 或 http://www.cnemergency.org.cn/CN/Y2018/V38/I9/827

［1］Chouchani ET, Pell VR, James AM, et al. A Unifying Mechanism for Mitochondrial Superoxide Production during Ischemia-Reperfusion Injury［J］. Cell Metab, 2016, 23(2):254-263. ［2］Lu Q, Tucker D, Dong Y, et al. Neuroprotective and Functional Improvement Effects of Methylene Blue in Global Cerebral Ischemia［J］. Mol Neurobiol, 2016, 53(8):5344-5355. ［3］Musatov A, Robinson NC. Susceptibility of mitochondrial electron-transport complexes to oxidative damage. Focus on cytochrome coxidase［J］. Free Radic Res, 2012, 46(11):1313-1326. ［4］Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release［J］. Physiol Rev, 2014, 94(3):909-950. ［5］Raz L, Zhang QG, Zhou CF, et al. Role of Rac1 GTPase in NADPH oxidase activation and cognitive impairment following cerebral ischemia in the rat［J］. PloS One, 2010, 5(9):e12 606. ［6］Lu Q, Wainwright MS, Harris VA, et al. Increased NADPH oxidase-derived superoxide is involved in the neuronal cell death induced by hypoxia-ischemia in neonatal hippocampal slice cultures［J］. Free Radic Biol Med, 2012, 53(5):1139-1151. ［7］Brookes PS, Yoon Y, Robotham JL, et al. Calcium, ATP, and ROS: a mitochondrial love-hate triangle［J］. Am J Physiol Cell Physiol, 2004, 287(4):C817-833. ［8］Kalogeris T, Bao Y, Korthuis RJ. Mitochondrial reactive oxygen species: A double edged sword in ischemia/reperfusion vs preconditioning［J］. Redox Biol, 2014, 2(1):702-714. ［9］Chan PH. Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia［J］. Neurochem Res, 2004, 29 (11): 1943-1949. ［10］Chen H, Yoshioka H, Kim GS, et al. Oxidative stress in ischemic brain damage: mechanisms of cell death and potential molecular targets for neuroprotection［J］. Antioxid Redox Signal, 2011, 14(8):1505-1517.［11］Sanderson TH, Reynolds CA, Kumar R, et al. Molecular Mechanisms of Ischemia-Reperfusion Injury in Brain: Pivotal Role of the Mitochondrial Membrane Potential in Reactive Oxygen Species Generation［J］. Mol Neurobiol, 2013, 47(1):9-23. ［12］Wang Q, Tang XN, Yenari MA. The inflammatory response in stroke［J］. J Neuroimmunol, 2007, 184(1-2):53-68. ［13］del Zoppo G, Ginis I, Hallenbeck JM, et al. Inflammation and stroke: putative role for cytokines, adhesion molecules and iNOS in brain response to ischemia［J］. Brain Pathol, 2000, 10(1):95-112. ［14］Denes A, Wilkinson F, Bigger B, et al. Central and haematopoietic interleukin-1 both contribute to ischaemic brain injury in mice［J］. Dis Model Mech, 2013, 6(4):1043-1048. ［15］Pradillo JM, Denes A, Greenhalgh AD, et al. Delayed administration of interleukin-1 receptor antagonist reduces ischemic brain damage and inflammation in comorbid rats［J］. J Cereb Blood Flow Metab, 2012, 32(9):1810-1819. ［16］Yuan J. Neuroprotective strategies targeting apoptotic and necroticcell death for stroke［J］. Apoptosis, 2009, 14(4):469-477. ［17］Chen CH, Jiang Z, Yan JH, et al. The involvement of programmed cell death 5 (PDCD5) in the regulation of apoptosis in cerebral ischemia/reperfusion injury［J］. CNS Neurosci Ther, 2013, 19(8):566-576. ［18］Rossé T, Olivier R, Monney L, et al. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c［J］. Nature, 1998, 391(6666):496-499. ［19］Maharjan S, Oku M, Tsuda M, et al. Mitochondrial impairment triggers cytosolic oxidative stress and cell death following proteasome inhibition［J］. Sci Rep, 2014, 4:5896. ［20］Ge P, Luo Y, Liu CL, et al. Protein aggregation and proteasome dysfunction after brain ischemia［J］. Stroke, 2007, 38(12):3230-3236. ［21］Massaad CA. Neuronal and vascular oxidative stress in Alzheimer′sdisease［J］. Curr Neuropharmacol, 2011, 9(4):662-673. ［22］Lee CH, Yan B, Yoo KY, et al. Ischemia-induced changes in glucagon-like peptide-1 receptor and neuroprotective effect of its agonist, exendin-4, in experimental transient cerebral ischemia［J］. J Neurosci Res, 2011, 89(7):1103-1113. ［23］Atamna H, Kumar R. Protective role of methylene blue in Alzheimer′s disease via mitochondria and cytochrome coxidase［J］. J Alzheimers Dis, 2010, 20 (Suppl 2):S439-452. ［24］Ohlow MJ, Moosmann B. Phenothiazine: the seven lives of pharmacology′s first lead structure［J］. Drug Discov Today, 2011, 16(3-4):119-131. ［25］Rojas JC, Simola N, Kermath BA, et al. Striatal neuroprotection with methylene blue［J］. Neuroscience, 2009, 163(3):877-889. ［26］Rojas JC, John JM, Lee J, et al. Methylene Blue Provides Behavioral and Metabolic Neuroprotection Against Optic Neuropathy［J］. Neurotoxicity Research, 2009, 15(3):260-273. ［27］Pelgrims J, De Vos F, Van den Brande J, et al. Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: Report of 12 cases and a review of the literature［J］. Br J Cancer, 2000, 82(2):291-294. ［28］Roy Choudhury G, Winters A, Rich RM, et al. Methylene blue protects astrocytes against glucose oxygen deprivation by improving cellular respiration［J］. PloS One, 2015, 10(4):e0 123 096. ［29］Muratsubaki H, Yajima N, Yoneda H, et al. Methylene blue protection against hypoxic injury in primary cultures of rat hepatocyte monolayers［J］. Cell Biochem Funct, 2008, 26(2):275-278. ［30］Oz M, Lorke DE, Petroianu GA. Methylene blue and Alzheimer′s disease［J］. Biochemical Pharmacology, 2009, 78(8):927-932. ［31］Di Y, He YL, Zhao T, et al. Methylene Blue Reduces Acute Cerebral Ischemic Injury via the Induction of Mitophagy［J］. Mol Med, 2015, 21:420-429. ［32］Wen Y, Li W, Poteet EC, et al. Alternative Mitochondrial Electron Transfer as a Novel Strategy for Neuroprotection［J］. J Biol Chem, 2011, 286(18):16 504-16 515. ［33］Jiang Z,Watts LT,Huang S,et al. The Effects of Methylene Blue on Autophagy and Apoptosis in MRI-Defined Normal Tissue, Ischemic Penumbra and Ischemic Core［J］. PLoS One, 2015, 10 (6), e0 131 929. ［34］Shen Q, Du F, Huang S, et al. Neuroprotective efficacy of methylene blue in ischemic stroke: an MRI study［J］. PloS One, 2013, 8(11):e79 833. ［35］Young GB. Clinical practice. Neurologic prognosis after cardiac arrest［J］. N Engl J Med, 2009, 361(6):605-611. ［36］Colbourne F, Sutherland G, Corbett D. Postischemic hypothermia. A critical appraisal with implications for clinical treatment［J］. Mol Neurobiol, 1997, 14(3):171-201. ［37］Miclescu A, Sharma HS, Martijn C, et al. Methylene blue protects the cortical blood-brain barrier against ischemia/reperfusion-induced disruptions［J］. Crit Care Med, 2010, 38(11):2199-2206. ［38］Sharma HS, Miclescu A, Wiklund L. Cardiac arrest-induced regional blood-brain barrier breakdown, edema formation and brain pathology: a light and electron microscopic study on a new model for neurodegeneration and neuroprotection in porcine brain［J］. J Neural Transm(Vienna), 2011, 118(1):87-114. ［39］Gabrielli D, Belisle E, Severino D, et al. Binding, aggregation and photochemical properties of methylene blue in mitochondrial suspensions［J］. Photochem Photobiol, 2004, 79(3):227-232. ［40］Atamna H, Nguyen A, Schultz C, et al. Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways［J］. FASEB J, 2008, 22(3):703-712. ［41］de la Torre JC, Cada A, Nelson N, et al. Reduced cytochrome oxidase and memory dysfunction after chronic brain ischemia in aged rats［J］. Neurosci Lett, 1997, 223(3):165-168. ［42］Callaway NL, Riha PD, Wrubel KM, et al. Methylene blue restores spatial memory retention impaired by an inhibitor of cytochrome oxidase in rats［J］. Neurosci Lett, 2002, 332(2):83-86. ［43］Poteet E, Winters A, Yan LJ, et al. Neuroprotective actions of methylene blue and its derivatives［J］. PloS One, 2012, 7(10):e48 279. ［44］Brinkkoetter PT, Song H, L sel R, et al. Hypothermic injury: the mitochondrial calcium, ATP and ROS love-hate triangle out of balance［J］. Cell Physiol Biochem, 2008, 22(1-4):195-204. ［45］Tian WF, Zeng S, Sheng Q, et al. Methylene Blue Protects the Isolated Rat Lungs from Ischemia-Reperfusion Injury by Attenuating Mitochondrial Oxidative Damage［J］. Lung, 2018,196(1):73-82. ［46］Li P, He QP, Ouyang YB, et al. Early release of cytochrome C and activation of caspase-3 in hyperglycemic rats subjected to transient forebrain ischemia［J］. Brain Res, 2001, 896(1-2):69-76. ［47］Ikeda Y, Shirakabe A, Maejima Y, et al. Endogenous Drp1 mediates mitochondrial autophagy and protects the heart against energy stress Novelty and significance［J］. Circulation Research, 2015, 116(2):264-278. ［48］Wu H, Xue D, Chen G, et al. The BCL2L1 and PGAM5 axis defines hypoxia-induced receptor-mediated mitophagy［J］. Autophagy, 2014, 10(10):1712-1725. ［49］Kubli DA, Gustafsson B. Mitochondria and mitophagy: the yin and yang of cell death control［J］. Circ Res, 2012, 111(9):1208-1221. ［50］Feng X, Liu X, Zhang W, et al. p53 directly suppresses BNIP3 expression to protect against hypoxia-induced cell death［J］. EMBO J,2011, 30(16): 3397-3415. ［51］Tasdemir E, Maiuri MC, Galluzzi L, et al. Regulation of autophagyby cytoplasmic p53［J］. Nat Cell Biol, 2008, 10(6):676-687. ［52］Xie L, Li W, Winters A, et al. Methylene blue induces macroautophagy through 5′ adenosine monophosphate-activated protein kinase pathway to protect neurons from serum deprivation［J］. Front Cell Neurosci, 2013, 7:56. ［53］Fenn AM, Skendelas JP, Moussa DN, et al. Methylene blue attenuates traumatic brain injury-associated neuroinflammation and acute depressive-like behavior in mice［J］. J Neurotrauma,2015, 32(2):127-138. ［54］Kwilasz AJ, Grace PM, Serbedzija P, et al. The therapeutic potential of interleukin-10 in neuroimmune diseases［J］. Neuropharmacology, 2015, 96(Pt A):55-69. ［55］Bachis A, Colangelo AM, Vicini S, et al. Interleukin-10 prevents glutamate-mediated cerebellar granule cell death by blocking caspase-3-like activity［J］. J Neurosci, 2001, 21(9):3104-3112. ［56］Zhou Z, Peng X, Insolera R, et al. Interleukin-10 provides direct trophic support to neurons［J］. J Neurochem, 2009, 110(5):1617-1627. ［57］Boyd ZS, Kriatchko A,Yang J,et al. Interleukin-10 receptor signaling through STAT-3 regulates the apoptosis of retinal ganglion cells in response to stress［J］. Invest Ophthalmol Vis Sci, 2003, 44 (12), 5206-5211. ［58］Sharma S, Yang B, Xi X, et al. IL-10 directly protects cortical neurons by activating PI-3 kinase and STAT-3 pathways［J］. Brain Res, 2011, 1373:189-194. ［59］Turovskaya MV, Turovsky EA, Zinchenko VP, et al. Interleukin-10 modulates ［Ca2+］i response induced by repeated NMDA receptor activation with brief hypoxia through inhibition of InsP(3)-sensitive internal stores in hippocampal neurons［J］. Neurosci Lett, 2012, 516(1):151-155. ［60］Obrenovitch TP, Urenjak J. Altered glutamatergic transmission in neurological disorders: From high extracellular glutamate to excessive synaptic efficacy［J］. Prog Neurobiol, 1997, 51(1):39-87. ［61］Iadecola C. Bright and dark sides of nitric oxide in ischemic brain injury［J］. Trends Neurosci, 1997, 20(3):132-139. ［62］Samdani AF, Dawson TM, Dawson VL. Nitric oxide synthase in models of focal ischemia［J］. Stroke, 1997, 28(6):1283-1288. ［63］Dawson VL, Dawson TM. Nitric oxide neurotoxicity［J］. J Chem Neuroanat, 1996, 10(3-4):179-190. ［64］Huang C, Tong L, Lu X, et al. Methylene Blue Attenuates iNOS Induction Through Suppression of Transcriptional Factor Binding Amid iNOS mRNA Transcription［J］. J Cell Biochem, 2015, 116(8):1730-1740. ［65］Jiang MH, Kaku T, Hada J, et al. Different effects of eNOS and nNOS inhibition on transient forebrain ischemia［J］. Brain Res, 2002, 946(1):139-147. ［66］Wolin MS, Cherry PD, Rodenburg JM, et al. Methylene blue inhibits vasodilation of skeletal muscle arterioles to acetylcholine and nitric oxide via the extracellular generation of superoxide anion［J］. J Pharmacol Exp Ther, 1990, 254(3):872-876. ［67］Gruetter CA, Kadowitz PJ, Ignarro LJ. Methylene blue inhibits coronary arterial relaxation and guanylate cyclase activation by nitroglycerin, sodium nitrite, and amyl nitrite［J］. Can J Physiol Pharmacol, 1981, 59(2):150-156. ［68］Mayer B, Brunner F, Schmidt K. Inhibition of nitric oxide synthesis by methylene blue［J］. Biochem Pharmacol, 1993, 45(2):367-374. ［69］Wei G, Dawson VL, Zweier JL. Role of neuronal and endothelial nitric oxide synthase in nitric oxide generation in the brain following cerebral ischemia［J］. Biochim Biophys Acta, 1999, 1455(1):23-34.