缺血预处理对脑缺血再灌注损伤保护作用的研究进展

神经药理学报 ›› 2015, Vol. 5 ›› Issue (5): 57-64.

• 综述 • 上一篇

缺血预处理对脑缺血再灌注损伤保护作用的研究进展

张婧，邹玉安，董晓华

1. 河北北方学院，张家口，075000，中国
2. 河北北方学院附属第一医院，张家口，075000，中国

出版日期:2015-10-26 发布日期:2016-03-03
通讯作者: 邹玉安，男，教授，硕士，研究生导师；研究方向：脑血管病；E-mail：zya8857111@sohu.com 董晓华，女，教授，博士，研究生导师；研究方向：神经药理学；E-mail：hbdxh76@163.com
作者简介:张婧，女，硕士研究生；研究方向：神经药理学；E-mail：2393336558@qq.com
基金资助:
河北省卫生厅课题基金资助项目（No.20090591、No.2016035），河北省高等学校科学技术研究重点项目（No.ZD2014065）

Research Progress on the Protective Eff ect of Cerebral Ischemia Preconditioning on Cerebral Ischemia Injury

ZHANG Jing, ZOU Yu-an, Dong Xiao-hua

1. Hebei North University，Zhangjiakou，075000，China
2. The First Affiliated Hospital of Hebei North University，Zhangjiakou，075000，China

Online:2015-10-26 Published:2016-03-03
Contact: 邹玉安，男，教授，硕士，研究生导师；研究方向：脑血管病；E-mail：zya8857111@sohu.com 董晓华，女，教授，博士，研究生导师；研究方向：神经药理学；E-mail：hbdxh76@163.com
About author:张婧，女，硕士研究生；研究方向：神经药理学；E-mail：2393336558@qq.com
Supported by:
河北省卫生厅课题基金资助项目（No.20090591、No.2016035），河北省高等学校科学技术研究重点项目（No.ZD2014065）

摘要/Abstract

摘要： 脑缺血预处理(cerebral ischemia preconditioning, CIP)是指对脑组织采用机械刺激，如一次或多次短暂性、非致死性脑缺血再灌注刺激，启动脑组织产生内源性保护机制，将对致死性的缺血产生显著的耐受，从而减弱或阻止脑缺血缺氧引起的级联反应。这种现象又称为脑缺血耐受(Cerebral ischemia tolerance,CIT)。脑缺血再灌注损伤(cerebral ischemia-reperfusion injury，CIRI)是一种多种机制参与的临床病理生理过程，是指脑缺血导致脑细胞损伤，恢复血流再灌注后，其组织损伤和功能障碍反而进一步加重甚至发生不可逆性损伤的现象。脑缺血预处理对脑缺血再灌注损伤具有保护作用，该文就脑缺血预处理对脑缺血再灌注损伤保护作用的相关神经保护机制及重要通路进行综述。

关键词: 脑缺血预处理, 再灌注损伤\自噬, 炎症, 钙超载

Abstract: Cerebral ischemic preconditioning（ CIP） is a method of endogenous mechanical stimulation of cerebral tissue，such as inducing the reperfusion stimulation by once，or repeatedly transient cerebral ischemia and non-fatal cerebral ischemia. In this way the cerebral tissue will produce the endogenesis defense mechanism.The cerebral tissue will generate significant tolerance of lethal ischemia，and weaken or block the cascade reaction induced by cerebral ischemia or cerebral anoxia. And this phenomenon is also called cerebral ischemia tolerance （CIT）. Cerebral ischemia-reperfusion injury（CIRI） is a physiological process of clinical pathology that is involoved in multipal mechanism. It could further aggravate the extent of cerebral tissue damage and dysfunction，and even irreversible damage occurs after restoration of blood flow and reperfusion. All in all，CIP plays a protective role to CIRI. This review will summarize the related neural protection mechanism and important pathways about CIP for CIRI protection.

Key words: cerebral ischemia preconditioning, ischemia-reperfusion injury, autophagy, inflammation, calcium overload

张婧，邹玉安，董晓华. 缺血预处理对脑缺血再灌注损伤保护作用的研究进展[J]. 神经药理学报, 2015, 5(5): 57-64.

ZHANG Jing, ZOU Yu-an, Dong Xiao-hua. Research Progress on the Protective Eff ect of Cerebral Ischemia Preconditioning on Cerebral Ischemia Injury[J]. Acta Neuropharmacologica, 2015, 5(5): 57-64.

参考文献

[1]Mirjana Jovicevic, Ivana Divjak, Petar Slankamenac, et al. The most frequent causes of ischemic stroke in young adults[J]. Med Pregl, 2011, 64(5-6): 331-335.

[2]Grant C Sorkin, Travis M Dumont, Maxim Mokin, et al. Hyperacute carotid stent thrombosis during emergent revascularization treated with intraarterial eptifibatide after systemic administration of recombinant tissue plasminogen activator[J]. J Vasc Interv Neurol, 2015, 8(3):50-55.

[3] Kazuo Kitagawa, Masayasu Matsumoto, Tagaya M, et al. Ischemic tolerance phenomenon found in the brain [J].Brain Res, 1990, 528(1): 21-24.

[4]Michiko Nakamura, Kazuhiko Nakakimura, Mishiya Matsumoto, et al. Rapid tolerance to focal cerebral ischemia in rats is attenuated by adenosine A1receptor antagonist[J].Cereb Blood Flow Metab, 2002, 22(2) :161-170.

[5]Tulin Alkan, Bulent Goren, Ebru Vatansever, et al. Effects of hypoxic preconditioning in antioxidant enzyme activities in hypoxic-ischemic brain damage in immature rats[J]. Turk Neurosurg, 2008, 18(2): 165-171.

[6]Wang Rui-min, Yang Fang, Zhang Yu-xin. Preconditioning-induced activation of ERK5 is dependent on moderate Ca influx via NMDA receptors and contributes to ischemic tolerance in the hippocampal CA1 region of rats[J].Life Sci, 2006, 79(19): 1839-1846.

[7]Cornelia Kiewert, Joachim Hartmann, James Stoll, et al.NGP1-01 is a brain-permeable dual blocker of neuronal voltage-and ligand-operated calcium channels[J].Neurochem Res, 2006, 31(3):395-399.

[8]Kunjan R Dave, Richard Anthony DeFazio, Ami P Raval, et al. Ischemic preconditioning targets the respiration of synaptic mitochondria via protein kinase Cε[J]. J Neurosci, 2008, 28(16): 4172-4182.

[9]Cinzia Costa, Giuseppina Martella, Barbara Picconi, et al. Multiple mechanisms underlying the neuroprotective effects of antiepileptic drugs against in vitro ischemia[J].Stroke, 2006, 37 (5):1319-1326.

[10]Joseph S Tauskela, Balu R chakravarthy, Christine L Murray, et al. Evidence from cultured rat cortical neurons of differences in the mechanism of ischemic preconditioning of brain and heart[J]. Brain Res, 1999, 827(1-2): 143-151.

[11]Zhou Mian, Christie M Wang, Yang Weng-lang, et al. Microglial CD14 activated by iNOS contributes to neuroinflammation in cerebral ischemia[J].Brain Res, 2013, 1506: 105-114.

[12]Hu Xiao-rong, Jiang Hong, Cui Bo, et al. Preconditioning with high mobility group box 1 protein protects against myocardial ischemia-reperfulion injury[J].Int J Cardio, 2010, 145(1): 111-112.

[13]Gong Gu, Bai Shu-rong, Wu Wei, et al. Lrg participates in lipopolysaccharide preconditioning-induced brain ischemia injury via TLR4 signaling pathway[J].Mol Neurosci, 2014, 54(1): 20-26.

[14]Khacho P, Wang B, Ahlskog N, et al. Differential effects of N-acetyl -aspartyl-glutamate on synaptic and extrasynaptic NMDA receptors are subunit- and pH-dependent in the CA1 region of the mouse hippocampus[J].Neurobiol Dis, 2015, 82: 580-592.

[15]He Yong, William G M Janssen, Jeffrey D Rothstein, et al. Differential synaptic localization of the glutamate transporter EAAC1 and glutamate receptor subunit GIuR2 in the rat hippocampus[J]. Comp Neurol, 2000, 418(3): 255-269.

[16]Yi-Bing Ouyang, Xu Li-Jun, Liu Si-wei, et al. Role of astrocytes in delayed neuronal death: GLT-1 and its novel regulation by MicroRNAs[J]. Adv Neurobiol, 2014, 11:171-188.

[17]Daniel Zemke, Jeremy L Smith, Mathew Reeves, et al. Ischemia and ischemic tolerance in the brain:an overview[J].Neurotoxicology, 2004, 25(6): 895-904.

[18]Brad R S Broughton, David C Reutens, Christopher G Sobey. Apoptotic mechanisms after cerebral ischemia[J]. Stroke, 2009, 40(5): e331-e339.

[19] Julien Puyal, Anne Vaslin, Vincent Mottier, et al. Postischemic treatment of neonatal cerebral ischemia should target autophagy[J].Ann Neurol, 2009, 66 (3):378-389.

[20]Hoyer-Hansen M, Jaattela M. Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium[J]. Cell Death Differ, 2007, 14(9): 1576-1582.

[21]Yutaka Matsui, Hiromitsu Takagi, Qu Xue-ping, et al. Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy[J].Circ Res, 2007, 100 (6): 914-922.

[22]Yasuo Uchiyama, Masato Koike, Masahiro Shibata, et al. Autophagic neuron death in neonatal brain ischemia/hypoxia[J].Autophagy, 2008, 4(4): 404-408.

[23]Fatemeh Zare Mehrjerdi, Nahid Aboutaleb, Rouhollah Habibey, et al. Increased phosphorylation of mTOR is involved in remote ischemic preconditioning of hippocampus in mice[J]. Brain Res, 2013, 1526(12): 94-101.

[24]Hee-Kwon Park, Kon Chu, Keun-Hwa Jung, et al. Autophagy is involved in the ischemic preconditioning[J].Neurosci Lett, 2009, 451(1):16-19.

[25]Zhang Min, Gong Jian-xue, Wang Jia-lei, et al. p38 MAPK participates in the mediation of GLT-1 up-regulation during the induction of brain ischemic tolerance by cerebral ischemic preconditioning[J].Mol Neurobiol, 2016, 2016: 1-14.

[26]Liu Ya-jing, Pan Qun-wen, Zhao Yu-hui, et al. MicroRNA-155 regulates ROS production, NO generation, apoptosis and multiple functions of human brain microvessel endothelial cells under physiological and pathological conditions[J].J Cell Biochem, 2015, 116(12): 2870-2881.

[27]Carles Justicia, Cecilla Gabriel, Anna M Planas. Activation of the JAK/STAT pathway following transient focal cerebral ischemia: signaling through Jak1 and Stat3 in astrocytes[J].Glia, 2000, 30(3): 253-270.

[28]Buddhadeb Dawn, Xuan Yu-ting, Guo Yiru, et al.IL-6 plays an obligatory role in late preconditioning via jak-stat signaling and upregulation of inos and cox-2[J].Cardiovasc Res, 2004, 64(1): 61-71.

[29]Shigeaki Suzuki, Kortaro Tanaka, Shigeru Nogawa, et al. Phosphorylation of signal transducer and activator of transcription-3(Stat3) after focal cerebral ischemia in rats[J]. Experimental Neurology, 2001, 170(1): 63-71.

[30]Yasushi Takagi, Jun Harada, Alberto Chiarugi, et al. Stat1 is activated in neurons after ischemia and contributes to ischemic brain injury[J].J Cereb Blood Flow Metab, 2002, 22(11): 1311-1318.

[31]Ebner F H, Sofia Mariotto, Elena Darra, et al. Use of STAT1 inhibitors in the treatment of brain I/R injury and neurodegenerative diseases[J].Cent Nerv Syst Agents Med Chem, 2011, 11(1): 2-7.

[32]Annett Spudich, Rico Frigg, Ertugrul Kilic, et al. Aggravation of ischemic brain injury by prion protein deficiency: role of erk-1/-2 and stat-1[J].Neurobiol Dis, 2005, 20(2): 442-449.

[33]Li Qin, Zhang Rui, Guo Yun-liang, et al. Effect of neuregulin on apoptosis and expressions of STAT3 and GFAP in rats following cerebral ischemic reperfusion[J]J Mol Neurosci, 2009, 37(1): 67-73.

[34]Roser Gorina, Coral Sanfeliu, Aida Galitó, et al. Exposure of glia to pro-oxidant agents revealed selective Stat1 activation by H2O2 and JAJ2-independent antioxidant features of the JAK2 inhibitor AG490[J].Glia, 2007, 55(13): 1313-1324.

[35]Irawan Satriotomo, Kellie K Bowen, Raghu Vemuganti, et al. JAK2 and STAT3 activation contributes to neuronal damage following transient focal cerebral ischemia[J]. J Neurochem, 2006, 98(5): 1353-1368.

[36]Wang Guan-song, Zhou De-shan, Wang Chang-zheng, et al. Hypoxic preconditioning suppresses group III secreted phospholipase A2-induced apoptosis via JAK2-STAT3 activation in cortical neurons[J]. J Neurochem, 2010, 114(4): 1039-1048.

[37]Gurfateh Singh, Ankur Rohilla, Manjeet Singh, et al. Possible role of JAK-2 in attenuated cardioprotective effect of ischemic preconditioning in hyperhomocysteinemic rat hearts[J]. Yakugaku Zasshi, 2009, 129(5): 523-535.

[38]Lou Yuan-lei, Guo Fei, Liu Fen, et al. MiR-210 activates notch signaling pathway in angiogenesis induced by cerebral ischemia[J].Mol Cell Biochem, 2012, 370(1-2): 45-51.

[39]Zhang Min, Gong Jian-xue, Wang Jia-lei.et al. p38 MAPK participates in the mediation of GLT-1 up-regulation during the induction of brain ischemic tolerance by cerebral ischemic preconditioning[J].Mol Neurobiol, 2016, 2016: 1-14.

[40]Cheng Yi-lin, Yuri Choi, Wei Lun Seow, et al. Evidence that neuronal Notch-1 promotes JNK/c-Jun activation and cell death following ischemic stress[J]. Brain Res, 2014, 1586: 193-202.

[41]Cheng Yi-lin, Jong-Sung Park, Silvia Manzanero, et al. Evidence that collaboration between HIF-1 and Notch-1 promotes neuronal cell death in ischemic stroke[J]. Neurobiol Dis, 2014, 62: 286-295.

[42]Sun Peng, Zhang Qing, Han Ji-Yuan, et al. TLR4 signaling induced TLR2 expression in the process of mimic cerebral ischemia/reperfusion in vitro[J].Sci China Life Sci, 2010, 53(2): 223-228.

[43]Antti Nurmi, Nina Vartiainen, Rea Pihlaja, et al. Pyrrolidine dithiocarbamate inhibits translocation of nuclear factor kappa-b in neurons and protects against brain ischaemia with a wide therapeutic time window[J].J Neurochem, 2004, 91(3): 755-765.

[44]Li WL, Yu SP, Chen D, et al. The regulatory role of NF-kappaB in autophagy-like cell death after focal cerebral ischemia in mice[J].Neuroscience, 2013, 244: 16-30.

[45]Macarena Hernandez-Jimenez, Olivia Hurtado, Maria Isabel Cuartero, et al. Silent information regulator 1 protects the brain against cerebral ischemic damage[J]. Stroke, 2013, 44(8): 2333-2337.

[46]李军, 曹红, 连庆泉, 等. ERK通路在脑缺血及缺血预处理沙土鼠海马神经元中的作用[J]. 中国应用生理学杂志, 2008, 24(2): 237-242.

[47]Hiroshi Kamada, Chikako Nito, Hidenori Endo, et al. Bad as a converging signaling molecule between survival pi3-k/akt and death jnk in neurons after transient focal cerebral ischemia in rats[J].J Cereb Blood Flow Metab, 2007, 27(3): 521-533.

[48]Zhao Ying-zheng, Lin Min, Lin Qian, et al. Intranasal delivery of bFGF with nanoliposomes enhances in vivo neuroprotection and neural injury recovery in a rodent stroke model[J].J Control Release, 2016, 224: 165-175.

[49]Ma Ming-ming, Wang Xue-jing, Ding Xue-bing, et al. Numb/ Notch signaling plays an important role in cerebral ischemia-induced apoptosis[J].Neurochem Res, 2013, 38(2): 254-261.

[50]Zhou Li, Ma Qi, Shi Hui-li, et al. NUMBL interacts with TRAF6 and promotes the degradation of TRAF6[J]. Biochem Biophys Res Commun, 2010, 392(3): 409-414.

[51]Tu Xian-kun, Yang Wei-zhong, Shi Song-sheng, et al. Spatio-temporal distribution of inflammatory reaction and expression of tlr2/4 signaling pathway in rat brain following permanent focal cerebral ischemia[J]. Neurochem Res, 2010, 35(8): 1147-1155.

[52]Zhang Peng, Cheng Guo-qiang, Chen Long-xia, et al. Cerebral hypoxia- ischemia increases toll-like receptor 2 and 4 expression in the hippocampus of neonatal rats[J].Brain Dev, 2015, 37(8): 747-752.

[53]Wang Yan-chun, Lin Sen, Yang Qing-wu. Toll-like receptors in cerebral ischemic inflammatory injury[J].J Neuroinflammation, 2011, 8: 140.

[54]Jesus M Pradillo, David Fernandez-Lopez, Isaac Garcia-Yebenes, et al. Toll-like receptor 4 is involved in neuroprotection afforded by ischemic preconditioning[J].J Neurochem, 2009, 109(1): 287-294.

[55]Li Si-jie, Ma Chun, Shao Guo, et al. Safety and feasibility of remote limb ischemic preconditioning in patients with unilateral middle cerebral artery stenosis and healthy volunteers[J]. Cell Transplant, 2015, 24(9): 1901-1911.

[56]Liu Zong-jian, Chen Chen, Li Xiao-rong, et al. Remote ischemic preconditioning-mediated neuroprotection against stroke is associated with significant alterations in peripheral immune responses[J].CNS Neurosci Ther, 2016, 22(1): 43-52.

缺血预处理对脑缺血再灌注损伤保护作用的研究进展

Research Progress on the Protective Eff ect of Cerebral Ischemia Preconditioning on Cerebral Ischemia Injury

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	海吉涛, 罗焕敏. 病原微生物与阿尔茨海默病相关性研究进展[J]. 神经药理学报, 2020, 10(4): 58-64.
[2]	林思梅, 周虹, 杨宝学. 高尿酸血症与慢性肾脏病相关性研究进展[J]. 神经药理学报, 2020, 10(2): 55-64.
[3]	朱东海，林娟，郭海彪，李楚源. 脑心清片对脂多糖诱导的BV-2 细胞的抗炎及抗凋亡作用[J]. 神经药理学报, 2018, 8(2): 37-37.
[4]	曾菊，程斌，程肖蕊，周文霞，张永祥. 基于LPS 诱导小鼠炎症模型的LW-AFC 抗炎作用研究[J]. 神经药理学报, 2018, 8(2): 49-49.
[5]	邹征强，程玉芳，汪海涛，周中振，陈佳佳，冯红方，徐江平. PDE4 抑制剂FCPR03 对LPS 诱导小鼠抑郁样行为的改善作用及其机制研究[J]. 神经药理学报, 2017, 7(3): 43-43.
[6]	张耀东，张碧琼，吴文宁，等. 慢性地塞米松对海马神经元损伤及NLRP-1炎症小体激活的影响[J]. 神经药理学报, 2017, 7(3): 47-47.
[7]	张碧琼，张耀东，吴文宁，等. 慢性地塞米松通过激活BK-NLRP1信号通路导致海马神经元损伤的研究[J]. 神经药理学报, 2017, 7(3): 48-48.
[8]	钟秋萍，钟佳宏，余汇，程玉芳，汪海涛，徐江平. 新型PDE4抑制剂FCPR16的抗抑郁作用及机制研究*[J]. 神经药理学报, 2017, 7(3): 57-57.
[9]	陈佳佳，冯红芳，钟佳宏，邹征强，汪海涛，徐江平. PDE4抑制剂FCPR16对局灶性脑缺血再灌注损伤大鼠的保护作用[J]. 神经药理学报, 2017, 7(2): 68-68.
[10]	王明磊，王文革，张俊红. 激发时间与哮喘小鼠气道炎症及气道重塑关系的实验研究[J]. 神经药理学报, 2017, 7(1): 29-37.
[11]	杜贯涛，张春腾，洪浩. 5- 脂氧合酶与阿尔茨海默病[J]. 神经药理学报, 2016, 6(5): 39-44.
[12]	王莎莎，张钊，张美金，胡金凤，陈乃宏. Nrf2/ARE信号通路在抑郁症中的研究进展[J]. 神经药理学报, 2016, 6(3): 32-37.
[13]	魏孟琳，田莉，王小琴，邹玉安，薛茜. 大鼠脑缺血预处理对缺血再灌注神经功能的影响[J]. 神经药理学报, 2016, 6(2): 7-13.
[14]	王欢欢，薛茜，邹玉安. 内源性抗氧化应激机制在缺血预处理与缺血再灌注损伤中的研究进展[J]. 神经药理学报, 2016, 6(2): 46-52.
[15]	王丽娜，龚其海，李菲，吴芹，石京山. 金钗石斛多糖减轻脂多糖诱导的大鼠学习记忆减退及机制研究[J]. 神经药理学报, 2016, 6(1): 1-8.