缺血后处理对减轻脑缺血再灌注损伤的治疗作用及机制研究
|
摘要
目的：研究缺血后处理对局灶性脑缺血再灌注引起的脑组织损伤与蛋白质氧化的作用。
方法：所有实验动物被随机地分为假手术组、缺血组和缺血后处理组。缺血模型通过大脑中动脉闭塞（MCAO）法获得；在缺血发生2小时后立即给予3个循环的30秒再灌注/30秒再闭塞的缺血后处理。脑梗塞大小通过TTC染色法测量。采用荧光法监测H2O2经过辣根过氧化物酶催化还原的产物与羟基乙酸苯酯形成的复合物来测量H2O2水平。超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性通过商品化试剂盒测定。蛋白酶体活性、蛋白碳酰（羰基）衍生物和高级蛋白氧化产物（AOPP）通过分光光度计测量。全部数据用x±s表示，并进行统计学分析。
结果：缺血后处理组使脑梗塞灶大小由37.91%±2.16%降至21.38%±1.65%(p<0.01)，蛋白碳酰（羰基）产物和高级氧化产物（AOPP）分别从15.61±1.92mmol/mg和11.64±1.92mmol/mg降至11.71±1.37mmol/mg和9.12±1.27mmol/mg，两者水平显著降低。与之相反，缺血后处理组的SOD和CAT活性明显升高，分别从78.45±1.62U/g和8.76±1.33U/g升高至96.24±11.37U/g和12.56±2.14U/g，蛋白酶体的活性也从65.22%±7.31%升高至84.63%±11.24%。
结论：我们的研究表明，缺血后处理通过降低蛋白氧化作用缩小脑梗塞灶，同时，可以把蛋白氧化作用作为预防脑损伤的一个潜在的靶点。
Objective: To investigate the effects of ischemic postconditioning on braininjury and protein oxidization in focal ischemia and reperfusion.
Methods: All the animals were divided randomly into sham-operated group,ischemia group and ischemic postconditioning group. Ischemia was produced byusing middle cerebral artery occlusion (MCAO), and ischemic post-conditioning wasperformed by using3cycles of30-second/30-second reperfusion/re-occlusion at theend of2hours ischemia. Brain infarction size was evaluated by TTC staining. Thelevel of H2O2was measured fluorimetrically by monitoring the oxidation ofp-hydroxy phenyl acetate coupled with enzymatic reduction of hydrogen peroxide byhorseradish peroxidase. Activities of superoxide dismutase and catalase wereassayed by using commercial kits. Proteasome activity, protein carbonyl derivativesand advanced oxidized protein products were measured spectrophotometrically. Allthe data are expressed as Mean±SD and analyzed statistically.
Results: Ischemic postconditioning made the size of brain infarction decreasefrom37.91%±2.16%to21.38%±1.65%(p<0.01), concomitant with significantreduction in the levels of protein carbonyl products and advanced oxidation proteinproducts from15.61±1.92mmol/mg protein and11.64±1.92mmol/mg protein to11.71±1.37mmol/mg protein and9.12±1.27mmol/mg protein, respectively. Bycontrast, activities of SOD and CAT were elevated respectively by ischemicpostconditioning from78.45±1.62U/g protein and8.76±1.33U/g to96.24±11.37U/g protein and12.56±2.14U/g protein, as well as proteasome activity increased from65.22%±7.31%to84.63%±11.24%.
Conclusion: Our study indicates that the reduction of brain infarct size isbenefited from the decreased protein oxidization due to ischemic postconditioning,and protein oxidization is a potential target for preventing cerebral injury.
方法：所有实验动物被随机地分为假手术组、缺血组和缺血后处理组。缺血模型通过大脑中动脉闭塞（MCAO）法获得；在缺血发生2小时后立即给予3个循环的30秒再灌注/30秒再闭塞的缺血后处理。脑梗塞大小通过TTC染色法测量。采用荧光法监测H2O2经过辣根过氧化物酶催化还原的产物与羟基乙酸苯酯形成的复合物来测量H2O2水平。超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性通过商品化试剂盒测定。蛋白酶体活性、蛋白碳酰（羰基）衍生物和高级蛋白氧化产物（AOPP）通过分光光度计测量。全部数据用x±s表示，并进行统计学分析。
结果：缺血后处理组使脑梗塞灶大小由37.91%±2.16%降至21.38%±1.65%(p<0.01)，蛋白碳酰（羰基）产物和高级氧化产物（AOPP）分别从15.61±1.92mmol/mg和11.64±1.92mmol/mg降至11.71±1.37mmol/mg和9.12±1.27mmol/mg，两者水平显著降低。与之相反，缺血后处理组的SOD和CAT活性明显升高，分别从78.45±1.62U/g和8.76±1.33U/g升高至96.24±11.37U/g和12.56±2.14U/g，蛋白酶体的活性也从65.22%±7.31%升高至84.63%±11.24%。
结论：我们的研究表明，缺血后处理通过降低蛋白氧化作用缩小脑梗塞灶，同时，可以把蛋白氧化作用作为预防脑损伤的一个潜在的靶点。
Objective: To investigate the effects of ischemic postconditioning on braininjury and protein oxidization in focal ischemia and reperfusion.
Methods: All the animals were divided randomly into sham-operated group,ischemia group and ischemic postconditioning group. Ischemia was produced byusing middle cerebral artery occlusion (MCAO), and ischemic post-conditioning wasperformed by using3cycles of30-second/30-second reperfusion/re-occlusion at theend of2hours ischemia. Brain infarction size was evaluated by TTC staining. Thelevel of H2O2was measured fluorimetrically by monitoring the oxidation ofp-hydroxy phenyl acetate coupled with enzymatic reduction of hydrogen peroxide byhorseradish peroxidase. Activities of superoxide dismutase and catalase wereassayed by using commercial kits. Proteasome activity, protein carbonyl derivativesand advanced oxidized protein products were measured spectrophotometrically. Allthe data are expressed as Mean±SD and analyzed statistically.
Results: Ischemic postconditioning made the size of brain infarction decreasefrom37.91%±2.16%to21.38%±1.65%(p<0.01), concomitant with significantreduction in the levels of protein carbonyl products and advanced oxidation proteinproducts from15.61±1.92mmol/mg protein and11.64±1.92mmol/mg protein to11.71±1.37mmol/mg protein and9.12±1.27mmol/mg protein, respectively. Bycontrast, activities of SOD and CAT were elevated respectively by ischemicpostconditioning from78.45±1.62U/g protein and8.76±1.33U/g to96.24±11.37U/g protein and12.56±2.14U/g protein, as well as proteasome activity increased from65.22%±7.31%to84.63%±11.24%.
Conclusion: Our study indicates that the reduction of brain infarct size isbenefited from the decreased protein oxidization due to ischemic postconditioning,and protein oxidization is a potential target for preventing cerebral injury.
引文
[1] Fields JD, Khatri P, Nesbit GM, et al: Meta-analysis of randomizedintra-arterial thrombolytic trials for the treatment of acute stroke due to middlecerebral artery occlusion. J Neurointerv Surg.2011.3:151-155.
[2] Tjoumakaris SI, Jabbour PM, Rosenwasser RH: Neuroendovascularmanagement of acute ischemic stroke. Neurosurg Clin N Am.2009.20:419-429.
[3] Sirangelo I, Irace G: Inhibition of aggregate formation as therapeutic target inprotein misfolding diseases: effect of tetracycline and trehalose. Expert OpinTher Targets.2010.14:1311-1321.
[4] Pengfei Ge, Bin Liu, Wenhai Fan,et al: Aggregation pattern of proteasome inthe injured neurons induced by transient cerebral ischemia. Chemical Researchin Chinese Universities.2011.27:249-253.
[5] Norris EH, Giasson BI: Role of oxidative damage in protein aggregationassociated with Parkinson's disease and related disorders. Antioxid RedoxSignal.2005.7:672-684.
[6] Jung T, Grune T: The proteasome and its role in the degradation of oxidizedproteins. IUBMB Life.2008.60:743-752.
[7] Niizuma K, Endo H, Chan PH: Oxidative stress and mitochondrialdysfunction as determinants of ischemic neuronal death and survival. JNeurochem.2009.109(Suppl1):133-138.
[8] Ge P, Luo Y, Liu C, et al: Protein Aggregation and Proteasome Dysfunctionafter Brain Ischemia. Stroke.2007.38:3230-3236.
[9] Zhao H, Sapolsky RM, Steinberg GK: Interrupting reperfusion as a stroketherapy: ischemic postconditioning reduces infarct size after focal ischemia inrats. J Cereb Blood Flow Metab.2006.26:1114-1121.
[10] Gao X, Ren C, Zhao H: Protective effects of ischemic postconditioningcompared with gradual reperfusion or preconditioning. J Neurosci Res.2008.86:2505-2511.
[11] Wang JY, Shen J, Gao Q, et al: Ischemic postconditioning protects againstglobal cerebral ischemia/reperfusion-induced injury in rats. Stroke.2008.39:983-890.
[12] Xing B, Chen H, Zhang M, et al: Ischemic postconditioning inhibits apoptosisafter focal cerebral ischemia/reperfusion injury in the rat. Stroke.2008.39:2362-2369.
[13] Xing B, Chen H, Zhang M, et al: Ischemic post-conditioning protects brainand reduces inflammation in a rat model of focal cerebral ischemia/reperfusion.J Neurochem.2008.105:1737-1745.
[14] Penna C, Mancardi D, Rastaldo R, et al: Cardioprotection: a radical view Freeradicals in pre and postconditioning. Biochim Biophys Acta.2009.1787:781-793.(1-14为引言文献)
[15]王维治，神经病学[M].第四版.北京：人民卫生出版社.2002:122.
[16]卫生部疾病预防控制局，中华医学会神经病分会.中国脑血管病防治指南
[M].北京：人民卫生出版社.2007:1.
[17]王忠诚，王忠诚神经外科学[M].武汉：湖北科学技术出版社.2005:844.
[18]顾兵，程翔，金建波，等.脑缺血动物模型及其实验治疗学应用[J].中国临床药理学与治疗学.2010.15(9):1074-1080.
[19]吉蕊，陈莉，吴玉林.(E)-3-(4-(2(二甲氨基)乙氧基)-3-甲氧苯基)丙烯酸对大鼠局灶性脑缺血的保护作用及机制[J].中国临床药理学与治疗学.2010.15(5):502-506.
[20] Chade AR, Lerman A, Lerman LO. Kidney in earlyatherosclerosis [J].Hypertension.2005.45:1042-1049.
[21]蔡俊颖，董强，付建辉.脑动脉狭窄或闭塞后侧支循环与卒中预后的关系[J].神经损伤与功能重建.2007.2:160-163.
[22] Liu PK, Grossman RG, Hsu CY, et al. Ischemic injury and faulty genetranscripts in the brain [J]. Trends Neurosci.2001.24(10):581-588.
[23]洪浩，刘国卿.缺血性脑血管疾病治疗的抗氧化应激策略[J].中国药理学通报.2004.20:19-24.
[24] Candelario-Jalil E. Injury and repair mechanisms in ischemic stroke:considerations for the development of novel neuro the rapeu-tics [J]. CurrOp inInvestig Drugs.2009.10(7):644-654.
[25] Hue RT, Padmaja S. The reaction of NO with superoxide [J]. Free Radic ResCommun.1993.18(4):195-199.
[26] Muramatsu K, Sheldon RA, Black SM, et al. Nitric oxide synthase activity andinhibition after neonatal hypoxia ischemia in the mouse brain [J]. Brain ResDev Brain Res.2000.123(2):119-127.
[27] Huang, PL. Neuronal and endothelial nitric oxide synthasegene knockout mice[J]. Braz J Med Biol Res.1999.32(11):1353-1359.
[28] Zhang ZG, Chopp M, Zabga C, Pollock JS, Forstermann U. Cerebral endo thelial nitric oxide synthase expression after foca l cerebral ische-miain rats [J].Stroke.1993.24(12):2016-2021. discussion2021-2012.
[29] Eliasson MJ, Huang Z, Ferrante RJ, Sasamata M, Molliver ME, Snyder SH, etal. Neuronal nitric oxide synthase activation and peroxynitrite formation inischemic stroke linked to neural damage [J]. JNeurosci.1999.19(14):5910-5918.
[30] Xu J, He L, Ahmed SH, et al. Oxygen-glucose deprivation induces induciblenitric oxide synthase and nitrityrosine ex-pression in cerebral endotheial cell [J].Stroke.2000.31(7):1744-1751.
[31] Bidmon HJ, Emde B, Kowalski T, et al. Nitric oxide syn-thase-I containingcortical interneurons co-express antiox-idative enzymes and anti-apoptoticBcl-2following focal is-chemia: evidence for direct and indirect mechanismstowards their resistance to neuropathology [J]. J Chem Neuroanat.2001.22(3):167-184.
[32] Iadecola C, Forster C, Nogawa S, Clark HB, Ross ME. Cyclooxygenase-2immunoreactivity in the human brain following cerebral ischemia [J]. ActaNeuropathol.1999.98(1):9-14.
[33] Breder CD, Ikwitt D, Kraig RP. Characterization of inducible cyclooxygenasein rat brain [J]. J Comp Neurol.1995.355(2):296-315.
[34] OB' rien PJ. Peroxidases [J]. Chem Biol In teract.2000.129(1-2):113-139.
[35] Chan PH, Kawase M, Murakami K, et al. Overexpression of SOD1intransgenic rats protects vulnerable neurons against is-chemic damage afterglobal cerebral ischemia and reperfusion [J]. J Neurosci.1998.18(20):8292-8299.
[36] Kim GW, Lewen A, Copin J, et al. The cytosolic antioxi-dant, copper/zincsuperoxide dismutase, attenuates blood-brain barrier disruption and oxidativecellular injury after pho-tothrombotic cortical ischemia in mice [J].Neuroscience.2001.105(4):1007-1018.
[37] Kawase M, Murakami K, Fujimura M, et al. Exacerbation of delayed cell injuryafter transient global ischemia in mutantmice with CuZn superoxide dismutasedeficiency [J]. Stroke.1999.30(9):1962-1968.
[38] Fujimura M, Morita-Fujimura Y, Kawase M, et al. Man-ganese superoxidedismutase mediates the early release of mi-tochondrial cytochromec andsubsequence DNA fagementation after permanent focal cerebral ischemia inmice [J]. J Neu-rosci.1999.19:3414-3422.
[39] Sheng H, Brady TC, Pearlstein RD, et al. Extracellular up-eroxide dismutasedeficiency worsens outcome from focal cere-bral ischemia in mouse [J].Neurosci Lett.1999.267(1):13-16.
[40] Sheng H, Kudo M, Mackensen GB, et al. Mice overexpress-ing extracellularsuperoxide dismutase have increased resis-tance to global cerebral ischemia [J].Exp Neurol.2000.163(2):392-398.
[41]张闻，罗勤慧.锰过氧化氢酶及其模型物研究进展[J].化学通报.2000.(10):4-7.
[42]李健，萤果撂，张社华.镁对血管内皮细胞缺氧再复氧损伤的保护作用[J].中国微循环.2003.7:227-229.
[43] S.K.Nelson, S.K.Bose, G.K.Grunward, The induction of human superoxidedismutase and catalase in vivo: a fundamentally new approach to antioxidanttherapy [J]. Free Radic. Biol. Med.2006.(40):341-347.
[44] Galluzzi L, MorselliE, Kepp O, Kroemer G. Targeting post-mitochon-drialeffectors of apoptosis for neuroprotection [J]. Biochim Biophys Acta.2009.1787(5):402-413.
[45] Reed JC, Kroemer G. Mechanisms of mitochondrialmembraneperme-abilization [J]. CellDeath Differ.2000.7(12):1145.
[46] Zamzami N, Kroemer G. The mitochondrion in apoptosis how Pandoras' boxopens [J]. NatRevMolCell Biol.2001.2(1):67-71.
[47] Joza N, Susin SA, Daugas E, Stanford WL, Cho SK, Li CY, et a l. E s-sentialrole of the mitochondrial apoptosis-inducing factor in pro-grammed cell death[J]. Nature.2001.410(6828):549-554.
[48] Nielsen M, Lambertsen KL, Clausen BH, Meldgaard M, Diemer NH, Zimmer J,et al. Nuclear tran slocation of endonuclease G in de-generating neurons afterpermanentm iddle cerebral artery occlusion in mice [J]. Exp Brain Res.2009.194(1):17-27.
[49] Sugawara T, Noshita N, Lewen A, Gasche Y, Ferrand-Drake M, Fujimura M, etal. Overexpression of copper/zinc superoxide dismutase in transgenic ratsprotects vu lnerable neurons against ischem ic damage by blocking themitochondrial pathway of caspase activation [J]. J Neurosci.2002.22(1):209-217.
[50] Siegelin M, Touzani O, Toutain J, Liston P, Rami A. Induction andredistribution of XAF1, a new antagonist of XIAP in the rat brain after transientfocal ischemia [J]. Neurobiol Dis.2005.20(2):509-518.
[51] Kaufman RJ, Stress signaling from the lumen of the endoplasmic reticulum:coordination of gene transcriptional and translational controls [J].Genes Dev.1999.13(10):1211-1233.
[52] Koumenis C, Wouters BG."Trans lating" tumor hypoxia: un folded proteinresponse (UPR)-dependent and UPR-independent path-ways [J]. Mol CancerRes.2006.4(7):423-436.
[53] Dalton TP, Shertzer HG, Puga A. Regulation of gene expres-sion by reactiveoxygen [J]. Annu Rev Pharmacol Toxicol.1999.39:67-101.
[54] Yu Z, Zhou D, Bruce-Keller AJ, et al. Lack of the p50submit of nuclearfactor-κB increase the vulnerability of hip-pocampal neurons to excitotoxicinjury [J]. J Neurosci.1999.19(20):8856-8865.
[55] Gasche Y, Copin JC, Sugawara T, et al. Matrix metallopro-teinase inhibitionprevents oxidative stress-associated blood-brain barrier disruption aftertransient focal cerebral ischemia [J]. J Cereb Blood Flow Metab.2001.21(12):1393-1400.
[56] Vollgraf U, Wegner M, Richter-Landsberg C. Activation of AP-1and nuclearfactor-kappa B transcription factors is in-volved in hydrogen peroxide-inducedapoptotic cell death of oligodendrocytes [J]. J Neurochem.1999.73(6):2501-2509.
[57] Huang CY, Fujimura M, Chang YY, et al. Overexpression of copper-zincsuperoxide dismutase attenuates acute activation of activator protein-1aftertransient focal cerebral ischemia in mice [J]. Stroke.2001.32(3):741-747.
[58] Fujimura M, Morita-Fujimura Y, Narasimhan P, et al. Copper-zinc superoxidedismutase prevents the early de-crease of apurinic/apyrimidinic endonucleaseand subsequent DNA fragmentation after transient focal cerebral ischemia inmice [J]. Stroke.1999.30(11):2408-2415.
[59] Greenamyre JT. The role of glutamate in neurotransmission and in neurologicdisease [J]. Arch Neurol.1986.43(10):1058-1063.
[60] Norberg E, Gogvadze V, Ott M, et al. An increase in intracellular Ca2+isrequired for the activation of mitochondrial calpain to re-lease AIF during celldeath [J]. Cell Death Differ.2008.15(12):1857-1864.
[61] Wu HY, Tomizawa K, Matsui H. Calpain-calcineurin signaling in thepathogenesis of calcium-dependent disorder [J]. Acta Med Okayama.2007.61(3):123-137.
[62] Koumura A, Nonaka Y, Hyakkoku K, et al. A novel calpain inhibi-tor,((1S)-1((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxo-propyl) amino) carbonyl)-3-methylbutyl) carbamic acid5-methoxy-3-oxapentylester, protects neuronalcells from cerebral ischemia-in-duced damage inmice [J]. Neuroscience.2008.157(2):309-318.
[63] Lian SL, Chen W, Raung SL, et al. Association of immune responses andischemic brain in farction in rat [J]. Neuroreport.2001.12(9):1943-1947.
[64] Ekdahl CT, Kokaia Z, Lindvall O. Brain in flammation and adult neurogenesis:The dual role of microglia [J]. Neuroscience.2009.158(3):1021-1029.
[65] Caso JR, Moro MA, Lorenzo P, et al. Involvement of IL-1beta in acutestress-induced worsening of cerebral is-chaemia in rats [J]. EurNeuropsychopharmacol.2007.17(9):600-607.
[66]鲁启洪.银杏活脑胶囊对大鼠缺血性脑卒中微血管增殖和神经干细胞再生的影响[J].湖北民族学院学报(医学版).2009.26(4):7-9.
[67] Sargis RM, Subbaiah PV. Protection of membrane cholester-ol bysphingomyelin against free radical-mediated oxidation [J].2006.40(12):2092-2102.
[68] P. T. David, M. J. Gerard. Photochem. Photobio1.1997.41(B):1-10.
[69] anisch KM, Milde J, Schempp H, et al. Vitamin C, vitaminE and flavonoids [J].Dev Ophthalmol.2005.38:59-69.
[70]李建喜，杨志强，王学智.活性氧自由基在动物机体内的生物学作用[J].动物医学进展.2006.27(10):33-36.
[71] Juranek I, Bezek S. Controversy of free radical hypothesis: re-active oxygenspecies-cause or consequence of tissue injury?[J]. Gen Physiol Biophys.2005.24(3):263-278.
[72] Calabrese V, Lodi R, Tonon C, et al. Oxidative stress, mito-chondrialdysfunction and cellular stress response in Fried-reich's ataxia [J]. J Neurol Sci.2005.233(1-2):145-162.
[73]李颖.治疗脑血管疾病的新抗氧化剂的设计和生物学评价.国外医药合成药、生化药、制剂分册.1998.19:71-74.
[74] Melidou M, Riganakos K, Galaris D. Protection against nu-clear DNA damageoffered by flavonoids in cells exposed to hydrogen peroxide: the role of ironchelation [J]. Free Radic Biol Med.2005.39(12):1591-1600.
[75]赵克然，杨毅军，曹道俊.氧自由基与临床[M].北京:中国医药科技大学出版社.2000:1-56.
[76] Djordjevic VB. Free radicals in cell biology [J]. Int Rev Cytol.2004.237:57-89.
[77] Kane DJ, Ord T, Anton R, et al. Expression of bcl-2inhibits necrotic neural celldeath [J]. Neurosci.1995.40(2):269-275.
[78]夏世钧，吴中亮.分子毒理学基础[M].武汉:湖北科学技术出版社.2001.
[79]孙存普，张建中，段绍瑾.自由基生物学导论[M].合肥:中国科学技术大学出版社.1999:19-20,29-30,226.
[80]李培峰，方允中.活性氧对蛋白质的损伤作用[J].生命的化学.1994.14(6):1-2.
[81] Michael J. Davies. Protein and peptide alkoxyl radicals can give rise toC-terminal decarboxylation and backbone cleavage [J]. Archives ofbiochemistry and biophysics.1996.336(1):163-172.
[82]文镜，张春华，董雨，等.蛋白质羰基含量与蛋白质氧化损伤[J].食品科学.2003.24(10):153-157.
[83]郑荣梁.自由基生物学[M].北京:高等教育出版社.1992.
[84] Thomas C. Squier. Oxidative stress and protein aggregation during biologicalaging [J]. Experimental Gerontology.2001.(36):1539-1550.
[85]李培峰.活性氧对铜锌超氧化物歧化酶的氧化修饰作用[J].生理科学进展.1995.26(1):50-52.
[86]李培峰，方允中，陈吉中，等.活性氧对蛋白质抗原与其相应抗体反应性增强的效应[J].中国免疫学杂志.1994.10(2):84-86.
[87] Stadtman ER, Levine RL. Free radical-mediated oxidation of free amino acidsand amino acid residues in proteins [J]. Ami-no Acids.2003.25(3-4):207-218.
[88] Stadtman ER. Metal ion-catalyzed oxidation of proteins biochemicalmechanism and biological consequences [J]. Free radicalbiology&Medicine.1990.9:315-325.
[89] Stadtman ER. Oxidation of free aminoacids and aminoacid residues in proteinsby radiolysis and by metal-catalyzed reaction [J]. AnnuRevBiochem.1993.62:797-821.
[90] Earl RStadtman, CNOliver. Metal-catalyzed oxidation of proteins [J]. JBiolChem.1991.266:2005-2008.
[91]文镜，李晶洁，郭豫，等.用蛋白质羰基含量评价抗氧化保健食品的研究[J].中国食品卫生杂志.2002.14(4):13-17.
[92] Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, et al. Advancedoxidation Protein Products as a novel marker of oxidative stress in uremia.Kidney Int.1996.49:1304-1313.
[93] Witko-Sarsat V, Friedlander M, Nguyen Khoa T, et al. Advanced oxidationProtein Products as novel mediators of inflammation and monocyte activationin chronic renal failure. J lmmunol.1998.161:2524-532.
[94] Wilkinson KD. Ubiquitination and deubiquitination: tar-geting of proteins fordegradation by the proteasome. Semin Cell Dev Biol.2000.11:141-148.
[95] Glickman MH, Maytal V. Regulating the26S pro2teasome [J]. Microbiol andImmunol.2002.268(2):43-47.
[96]何洪智，赵晓航，张立勇，等.蛋白质泛素化降解途径与肿瘤发生的关系[J].世界华人消化杂志.2002.10(12):1365-1368.
[97] Glickman MH. Getting in and out of the proteasome [J]. Semin Cell Dev Biol.2000.11(3):149-158.
[98] Martone ME, Jones YZ, Young SJ, Modification of postsynaptic densities aftertransient cerebral ischemia: a quantitative and three-dimensional ultrastructuralstudy. J Neurosci.1999.19:1988-1997.
[99] Hu BR, Martone ME, Jones YZ, et al. Protein aggregation after transientcerebral ischemia. J Neurosci.2000.20:3191-3199.
[100] Hu BR, Janelidze S, Ginsberg MD, et al. Protein aggregation after focal brainischemia and reperfusion. J Cereb Blood Flow Metab.2001.21:865-875.
[101] CN Oliver, AB ong-whan. Age-related changes in oxidized proteins [J]. TheJournal of Biological Chemistry.1987.262:5488-5491.
[102] CD Smith, JM Carney, PE Starke-Reed, et al. Excess brain Protein oxidationand enzyme dysfunction innormal aging and in Alzheimerdisease [J]. MedicalSciences.1991.88:10540-10543.
[103] Richter T, Munch G, Luth HJ, et al. Immunochemical crossreactivity ofantibodies specific for "advanced glycation endproducts" with "advancedlipoxidation endproducts"[J]. Neurobiol Aging.2005.26(4):465-474.
[104] Lyras L, Cairns NJ, Jenner A, et al. An assessment of oxidative damage toproteins, lipids and DNA in brain from patients with Alzheimer's disease [J].JNeurochem.1997.6(85):2061-2069.
[105] Dauer W, Przedborski S. Parkinson’s disease: mech-anisms and models [J].Neuron.2003.39:889-909.
[106] Basso M, Giraudo S, Corpillo D, et al. Proteomea-nalysis of human substantianigra in Parkinson’s dis-ease [J]. Proteomics.2004.4:3943-3952.
[107] Alam ZI, Daniel SE, Lees AJ, et al. Ageneralised in crease in proteincar-bonylsin the brain in Parkinson′s but not incidental Lewy body disease [J].JNeurochem.1997.69(3):1326-1329.
[108] Munch G, Luth HJ, Wong A, et al. Crosslinking of alpha-synuclein byadvanced glycation endproducts-an early pathophysiological step in Lewy bodyformation?[J]. Journal of Chemical Neuroanatomy.2000.20(3-4):253-257.
[109] Morabito F, Cristani M, Saija A, et al. Lipid peroxidation and protein oxidationin patients affected by Hodgkin's lymphoma [J]. Mediators Inflamm.2004.13(5-6):381-383.
[110] Ishii T, Yasuda K, Akatsuka A, et al. A mutation in the SDHC gene of complexII increases oxidative stress resulting in apoptosis and tumorigenesis [J]. CancerRes.2005.65(1):203-209.(15-110为综述文献)
[111] Longa EZ, Weinstein PR, Carlson S,et al. Reversible middle cerebral arteryocclusion without craniectomy in rats[J]. Stroke.1989.20(l):84-91.
[112] Xing BZ，Chen H，Zhang M，et al..Ischemic Post-conditioning protects brainand reduces inflammation in a rat model of focal cerebralischemia/reperfusion. JNeurochem.2008.105(5):1737-1745.
[113] Jolitha AB, Subramanyam MV, Asha Devi S: Modification by vitamin E andexercise of oxidative stress in regions of aging rat brain: studies on superoxidedismutase isoenzymes and protein oxidation status. Exp Gerontol.2006.41:753-763.
[114] Guo JY, Yang T, Sun XG, et al: Ischemic postconditioning attenuates liverwarm ischemia-reperfusion injury through Akt-eNOS-NO-HIF pathway. JBiomed Sci.2011.18:79.
[115] Liu KX, Li YS, Huang WQ, et al: Immediate postconditioning duringreperfusion attenuates intestinal injury. Intensive Care Med.2009.35:933-942.
[116] Zhou C, Tu J, Zhang Q, et al: Delayed ischemic postconditioning protectshippocampal CA1neurons by preserving mitochondrial integrity viaAkt/GSK3β signaling. Neurochem Int.2011.59:749-758.
[117] Prasad SS, Russell M, Nowakowska M: Neuroprotection induced in vitro byischemic preconditioning and postconditioning: modulation of apoptosis andPI3K-Akt pathways. J Mol Neurosci.2011.43:428-442.
[118] Wang Q, Zhang X, Ding Q, et al: Limb remote postconditioning alleviatescerebral reperfusion injury through reactive oxygen species-mediatedinhibition of delta protein kinase C in rats. Anesth Analg.2011.113:1180-1187.
[119] Zhang W, Miao Y, Zhou S, et al: Neuroprotective effects of ischemicpostconditioning on global brain ischemia in rats through upregulation ofhippocampal glutamine synthetase. J Clin Neurosci.2011.18:685-689.
[120] Yuan Y, Guo Q, Ye Z, et al: Ischemic postconditioning protects brain fromischemia/reperfusion injury by attenuating endoplasmic reticulumstress-induced apoptosis through PI3K-Akt pathway. Brain Res.2011.1367:85-93.
[121] Ji X, Luo Y, Ling F, et al: Mild hypothermia diminishes oxidative DNAdamage and pro-death signaling events after cerebral ischemia: a mechanismfor neuroprotection. Front Biosci.2007.12:1737-1747.
[122] Murín R, Drgová A, Kaplán P, et al: Ischemia/Reperfusion-induced oxidativestress causes structural changes of brain membrane proteins and lipids. GenPhysiol Biophys.2001.20:431-438.
[123] Shacter E: Quantification and significance of protein oxidation in biologicalsamples. Drug Metab Rev.2000.32:307-326.
[124] Lehotsky J, Murín R, Strapková A, et al: Time course ofischemia/reperfusion-induced oxidative modification of neural proteins in ratforebrain. Gen Physiol Biophys.2004.23:401-415.
[125] Murotomi K, Takagi N, Takeo S, et al: NADPH oxidase-mediated oxidativedamage to proteins in the postsynaptic density after transient cerebral ischemiaand reperfusion. Mol Cell Neurosci.2011.46:681-688.
[126]18Sugawara T, Chan PH. Reactive oxygen radicals and pathogenesis ofneuronal death after cerebral ischemia. Antioxid Redox Signal.2003.5:597-607.
[46] Zamzami N, Kroemer G. The mitochondrion in apoptosis how Pandoras' boxopens [J]. NatRevMolCell Biol.2001.2(1):67-71.
[47] Joza N, Susin SA, Daugas E, Stanford WL, Cho SK, Li CY, et a l. E s-sentialrole of the mitochondrial apoptosis-inducing factor in pro-grammed cell death[J]. Nature.2001.410(6828):549-554.
[48] Nielsen M, Lambertsen KL, Clausen BH, Meldgaard M, Diemer NH, Zimmer J,et al. Nuclear tran slocation of endonuclease G in de-generating neurons afterpermanentm iddle cerebral artery occlusion in mice [J]. Exp Brain Res.2009.194(1):17-27.
[49] Sugawara T, Noshita N, Lewen A, Gasche Y, Ferrand-Drake M, Fujimura M, etal. Overexpression of copper/zinc superoxide dismutase in transgenic ratsprotects vu lnerable neurons against ischem ic damage by blocking themitochondrial pathway of caspase activation [J]. J Neurosci.2002.22(1):209-217.
[50] Siegelin M, Touzani O, Toutain J, Liston P, Rami A. Induction andredistribution of XAF1, a new antagonist of XIAP in the rat brain after transientfocal ischemia [J]. Neurobiol Dis.2005.20(2):509-518.
[51] Kaufman RJ, Stress signaling from the lumen of the endoplasmic reticulum:coordination of gene transcriptional and translational controls [J].Genes Dev.1999.13(10):1211-1233.
[52] Koumenis C, Wouters BG."Trans lating" tumor hypoxia: un folded proteinresponse (UPR)-dependent and UPR-independent path-ways [J]. Mol CancerRes.2006.4(7):423-436.
[53] Dalton TP, Shertzer HG, Puga A. Regulation of gene expres-sion by reactiveoxygen [J]. Annu Rev Pharmacol Toxicol.1999.39:67-101.
[54] Yu Z, Zhou D, Bruce-Keller AJ, et al. Lack of the p50submit of nuclearfactor-κB increase the vulnerability of hip-pocampal neurons to excitotoxicinjury [J]. J Neurosci.1999.19(20):8856-8865.
[55] Gasche Y, Copin JC, Sugawara T, et al. Matrix metallopro-teinase inhibitionprevents oxidative stress-associated blood-brain barrier disruption aftertransient focal cerebral ischemia [J]. J Cereb Blood Flow Metab.2001.21(12):
[2] Tjoumakaris SI, Jabbour PM, Rosenwasser RH: Neuroendovascularmanagement of acute ischemic stroke. Neurosurg Clin N Am.2009.20:419-429.
[3] Sirangelo I, Irace G: Inhibition of aggregate formation as therapeutic target inprotein misfolding diseases: effect of tetracycline and trehalose. Expert OpinTher Targets.2010.14:1311-1321.
[4] Pengfei Ge, Bin Liu, Wenhai Fan,et al: Aggregation pattern of proteasome inthe injured neurons induced by transient cerebral ischemia. Chemical Researchin Chinese Universities.2011.27:249-253.
[5] Norris EH, Giasson BI: Role of oxidative damage in protein aggregationassociated with Parkinson's disease and related disorders. Antioxid RedoxSignal.2005.7:672-684.
[6] Jung T, Grune T: The proteasome and its role in the degradation of oxidizedproteins. IUBMB Life.2008.60:743-752.
[7] Niizuma K, Endo H, Chan PH: Oxidative stress and mitochondrialdysfunction as determinants of ischemic neuronal death and survival. JNeurochem.2009.109(Suppl1):133-138.
[8] Ge P, Luo Y, Liu C, et al: Protein Aggregation and Proteasome Dysfunctionafter Brain Ischemia. Stroke.2007.38:3230-3236.
[9] Zhao H, Sapolsky RM, Steinberg GK: Interrupting reperfusion as a stroketherapy: ischemic postconditioning reduces infarct size after focal ischemia inrats. J Cereb Blood Flow Metab.2006.26:1114-1121.
[10] Gao X, Ren C, Zhao H: Protective effects of ischemic postconditioningcompared with gradual reperfusion or preconditioning. J Neurosci Res.2008.86:2505-2511.
[11] Wang JY, Shen J, Gao Q, et al: Ischemic postconditioning protects againstglobal cerebral ischemia/reperfusion-induced injury in rats. Stroke.2008.39:983-890.
[12] Xing B, Chen H, Zhang M, et al: Ischemic postconditioning inhibits apoptosisafter focal cerebral ischemia/reperfusion injury in the rat. Stroke.2008.39:2362-2369.
[13] Xing B, Chen H, Zhang M, et al: Ischemic post-conditioning protects brainand reduces inflammation in a rat model of focal cerebral ischemia/reperfusion.J Neurochem.2008.105:1737-1745.
[14] Penna C, Mancardi D, Rastaldo R, et al: Cardioprotection: a radical view Freeradicals in pre and postconditioning. Biochim Biophys Acta.2009.1787:781-793.(1-14为引言文献)
[15]王维治，神经病学[M].第四版.北京：人民卫生出版社.2002:122.
[16]卫生部疾病预防控制局，中华医学会神经病分会.中国脑血管病防治指南
[M].北京：人民卫生出版社.2007:1.
[17]王忠诚，王忠诚神经外科学[M].武汉：湖北科学技术出版社.2005:844.
[18]顾兵，程翔，金建波，等.脑缺血动物模型及其实验治疗学应用[J].中国临床药理学与治疗学.2010.15(9):1074-1080.
[19]吉蕊，陈莉，吴玉林.(E)-3-(4-(2(二甲氨基)乙氧基)-3-甲氧苯基)丙烯酸对大鼠局灶性脑缺血的保护作用及机制[J].中国临床药理学与治疗学.2010.15(5):502-506.
[20] Chade AR, Lerman A, Lerman LO. Kidney in earlyatherosclerosis [J].Hypertension.2005.45:1042-1049.
[21]蔡俊颖，董强，付建辉.脑动脉狭窄或闭塞后侧支循环与卒中预后的关系[J].神经损伤与功能重建.2007.2:160-163.
[22] Liu PK, Grossman RG, Hsu CY, et al. Ischemic injury and faulty genetranscripts in the brain [J]. Trends Neurosci.2001.24(10):581-588.
[23]洪浩，刘国卿.缺血性脑血管疾病治疗的抗氧化应激策略[J].中国药理学通报.2004.20:19-24.
[24] Candelario-Jalil E. Injury and repair mechanisms in ischemic stroke:considerations for the development of novel neuro the rapeu-tics [J]. CurrOp inInvestig Drugs.2009.10(7):644-654.
[25] Hue RT, Padmaja S. The reaction of NO with superoxide [J]. Free Radic ResCommun.1993.18(4):195-199.
[26] Muramatsu K, Sheldon RA, Black SM, et al. Nitric oxide synthase activity andinhibition after neonatal hypoxia ischemia in the mouse brain [J]. Brain ResDev Brain Res.2000.123(2):119-127.
[27] Huang, PL. Neuronal and endothelial nitric oxide synthasegene knockout mice[J]. Braz J Med Biol Res.1999.32(11):1353-1359.
[28] Zhang ZG, Chopp M, Zabga C, Pollock JS, Forstermann U. Cerebral endo thelial nitric oxide synthase expression after foca l cerebral ische-miain rats [J].Stroke.1993.24(12):2016-2021. discussion2021-2012.
[29] Eliasson MJ, Huang Z, Ferrante RJ, Sasamata M, Molliver ME, Snyder SH, etal. Neuronal nitric oxide synthase activation and peroxynitrite formation inischemic stroke linked to neural damage [J]. JNeurosci.1999.19(14):5910-5918.
[30] Xu J, He L, Ahmed SH, et al. Oxygen-glucose deprivation induces induciblenitric oxide synthase and nitrityrosine ex-pression in cerebral endotheial cell [J].Stroke.2000.31(7):1744-1751.
[31] Bidmon HJ, Emde B, Kowalski T, et al. Nitric oxide syn-thase-I containingcortical interneurons co-express antiox-idative enzymes and anti-apoptoticBcl-2following focal is-chemia: evidence for direct and indirect mechanismstowards their resistance to neuropathology [J]. J Chem Neuroanat.2001.22(3):167-184.
[32] Iadecola C, Forster C, Nogawa S, Clark HB, Ross ME. Cyclooxygenase-2immunoreactivity in the human brain following cerebral ischemia [J]. ActaNeuropathol.1999.98(1):9-14.
[33] Breder CD, Ikwitt D, Kraig RP. Characterization of inducible cyclooxygenasein rat brain [J]. J Comp Neurol.1995.355(2):296-315.
[34] OB' rien PJ. Peroxidases [J]. Chem Biol In teract.2000.129(1-2):113-139.
[35] Chan PH, Kawase M, Murakami K, et al. Overexpression of SOD1intransgenic rats protects vulnerable neurons against is-chemic damage afterglobal cerebral ischemia and reperfusion [J]. J Neurosci.1998.18(20):8292-8299.
[36] Kim GW, Lewen A, Copin J, et al. The cytosolic antioxi-dant, copper/zincsuperoxide dismutase, attenuates blood-brain barrier disruption and oxidativecellular injury after pho-tothrombotic cortical ischemia in mice [J].Neuroscience.2001.105(4):1007-1018.
[37] Kawase M, Murakami K, Fujimura M, et al. Exacerbation of delayed cell injuryafter transient global ischemia in mutantmice with CuZn superoxide dismutasedeficiency [J]. Stroke.1999.30(9):1962-1968.
[38] Fujimura M, Morita-Fujimura Y, Kawase M, et al. Man-ganese superoxidedismutase mediates the early release of mi-tochondrial cytochromec andsubsequence DNA fagementation after permanent focal cerebral ischemia inmice [J]. J Neu-rosci.1999.19:3414-3422.
[39] Sheng H, Brady TC, Pearlstein RD, et al. Extracellular up-eroxide dismutasedeficiency worsens outcome from focal cere-bral ischemia in mouse [J].Neurosci Lett.1999.267(1):13-16.
[40] Sheng H, Kudo M, Mackensen GB, et al. Mice overexpress-ing extracellularsuperoxide dismutase have increased resis-tance to global cerebral ischemia [J].Exp Neurol.2000.163(2):392-398.
[41]张闻，罗勤慧.锰过氧化氢酶及其模型物研究进展[J].化学通报.2000.(10):4-7.
[42]李健，萤果撂，张社华.镁对血管内皮细胞缺氧再复氧损伤的保护作用[J].中国微循环.2003.7:227-229.
[43] S.K.Nelson, S.K.Bose, G.K.Grunward, The induction of human superoxidedismutase and catalase in vivo: a fundamentally new approach to antioxidanttherapy [J]. Free Radic. Biol. Med.2006.(40):341-347.
[44] Galluzzi L, MorselliE, Kepp O, Kroemer G. Targeting post-mitochon-drialeffectors of apoptosis for neuroprotection [J]. Biochim Biophys Acta.2009.1787(5):402-413.
[45] Reed JC, Kroemer G. Mechanisms of mitochondrialmembraneperme-abilization [J]. CellDeath Differ.2000.7(12):1145.
[46] Zamzami N, Kroemer G. The mitochondrion in apoptosis how Pandoras' boxopens [J]. NatRevMolCell Biol.2001.2(1):67-71.
[47] Joza N, Susin SA, Daugas E, Stanford WL, Cho SK, Li CY, et a l. E s-sentialrole of the mitochondrial apoptosis-inducing factor in pro-grammed cell death[J]. Nature.2001.410(6828):549-554.
[48] Nielsen M, Lambertsen KL, Clausen BH, Meldgaard M, Diemer NH, Zimmer J,et al. Nuclear tran slocation of endonuclease G in de-generating neurons afterpermanentm iddle cerebral artery occlusion in mice [J]. Exp Brain Res.2009.194(1):17-27.
[49] Sugawara T, Noshita N, Lewen A, Gasche Y, Ferrand-Drake M, Fujimura M, etal. Overexpression of copper/zinc superoxide dismutase in transgenic ratsprotects vu lnerable neurons against ischem ic damage by blocking themitochondrial pathway of caspase activation [J]. J Neurosci.2002.22(1):209-217.
[50] Siegelin M, Touzani O, Toutain J, Liston P, Rami A. Induction andredistribution of XAF1, a new antagonist of XIAP in the rat brain after transientfocal ischemia [J]. Neurobiol Dis.2005.20(2):509-518.
[51] Kaufman RJ, Stress signaling from the lumen of the endoplasmic reticulum:coordination of gene transcriptional and translational controls [J].Genes Dev.1999.13(10):1211-1233.
[52] Koumenis C, Wouters BG."Trans lating" tumor hypoxia: un folded proteinresponse (UPR)-dependent and UPR-independent path-ways [J]. Mol CancerRes.2006.4(7):423-436.
[53] Dalton TP, Shertzer HG, Puga A. Regulation of gene expres-sion by reactiveoxygen [J]. Annu Rev Pharmacol Toxicol.1999.39:67-101.
[54] Yu Z, Zhou D, Bruce-Keller AJ, et al. Lack of the p50submit of nuclearfactor-κB increase the vulnerability of hip-pocampal neurons to excitotoxicinjury [J]. J Neurosci.1999.19(20):8856-8865.
[55] Gasche Y, Copin JC, Sugawara T, et al. Matrix metallopro-teinase inhibitionprevents oxidative stress-associated blood-brain barrier disruption aftertransient focal cerebral ischemia [J]. J Cereb Blood Flow Metab.2001.21(12):1393-1400.
[56] Vollgraf U, Wegner M, Richter-Landsberg C. Activation of AP-1and nuclearfactor-kappa B transcription factors is in-volved in hydrogen peroxide-inducedapoptotic cell death of oligodendrocytes [J]. J Neurochem.1999.73(6):2501-2509.
[57] Huang CY, Fujimura M, Chang YY, et al. Overexpression of copper-zincsuperoxide dismutase attenuates acute activation of activator protein-1aftertransient focal cerebral ischemia in mice [J]. Stroke.2001.32(3):741-747.
[58] Fujimura M, Morita-Fujimura Y, Narasimhan P, et al. Copper-zinc superoxidedismutase prevents the early de-crease of apurinic/apyrimidinic endonucleaseand subsequent DNA fragmentation after transient focal cerebral ischemia inmice [J]. Stroke.1999.30(11):2408-2415.
[59] Greenamyre JT. The role of glutamate in neurotransmission and in neurologicdisease [J]. Arch Neurol.1986.43(10):1058-1063.
[60] Norberg E, Gogvadze V, Ott M, et al. An increase in intracellular Ca2+isrequired for the activation of mitochondrial calpain to re-lease AIF during celldeath [J]. Cell Death Differ.2008.15(12):1857-1864.
[61] Wu HY, Tomizawa K, Matsui H. Calpain-calcineurin signaling in thepathogenesis of calcium-dependent disorder [J]. Acta Med Okayama.2007.61(3):123-137.
[62] Koumura A, Nonaka Y, Hyakkoku K, et al. A novel calpain inhibi-tor,((1S)-1((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxo-propyl) amino) carbonyl)-3-methylbutyl) carbamic acid5-methoxy-3-oxapentylester, protects neuronalcells from cerebral ischemia-in-duced damage inmice [J]. Neuroscience.2008.157(2):309-318.
[63] Lian SL, Chen W, Raung SL, et al. Association of immune responses andischemic brain in farction in rat [J]. Neuroreport.2001.12(9):1943-1947.
[64] Ekdahl CT, Kokaia Z, Lindvall O. Brain in flammation and adult neurogenesis:The dual role of microglia [J]. Neuroscience.2009.158(3):1021-1029.
[65] Caso JR, Moro MA, Lorenzo P, et al. Involvement of IL-1beta in acutestress-induced worsening of cerebral is-chaemia in rats [J]. EurNeuropsychopharmacol.2007.17(9):600-607.
[66]鲁启洪.银杏活脑胶囊对大鼠缺血性脑卒中微血管增殖和神经干细胞再生的影响[J].湖北民族学院学报(医学版).2009.26(4):7-9.
[67] Sargis RM, Subbaiah PV. Protection of membrane cholester-ol bysphingomyelin against free radical-mediated oxidation [J].2006.40(12):2092-2102.
[68] P. T. David, M. J. Gerard. Photochem. Photobio1.1997.41(B):1-10.
[69] anisch KM, Milde J, Schempp H, et al. Vitamin C, vitaminE and flavonoids [J].Dev Ophthalmol.2005.38:59-69.
[70]李建喜，杨志强，王学智.活性氧自由基在动物机体内的生物学作用[J].动物医学进展.2006.27(10):33-36.
[71] Juranek I, Bezek S. Controversy of free radical hypothesis: re-active oxygenspecies-cause or consequence of tissue injury?[J]. Gen Physiol Biophys.2005.24(3):263-278.
[72] Calabrese V, Lodi R, Tonon C, et al. Oxidative stress, mito-chondrialdysfunction and cellular stress response in Fried-reich's ataxia [J]. J Neurol Sci.2005.233(1-2):145-162.
[73]李颖.治疗脑血管疾病的新抗氧化剂的设计和生物学评价.国外医药合成药、生化药、制剂分册.1998.19:71-74.
[74] Melidou M, Riganakos K, Galaris D. Protection against nu-clear DNA damageoffered by flavonoids in cells exposed to hydrogen peroxide: the role of ironchelation [J]. Free Radic Biol Med.2005.39(12):1591-1600.
[75]赵克然，杨毅军，曹道俊.氧自由基与临床[M].北京:中国医药科技大学出版社.2000:1-56.
[76] Djordjevic VB. Free radicals in cell biology [J]. Int Rev Cytol.2004.237:57-89.
[77] Kane DJ, Ord T, Anton R, et al. Expression of bcl-2inhibits necrotic neural celldeath [J]. Neurosci.1995.40(2):269-275.
[78]夏世钧，吴中亮.分子毒理学基础[M].武汉:湖北科学技术出版社.2001.
[79]孙存普，张建中，段绍瑾.自由基生物学导论[M].合肥:中国科学技术大学出版社.1999:19-20,29-30,226.
[80]李培峰，方允中.活性氧对蛋白质的损伤作用[J].生命的化学.1994.14(6):1-2.
[81] Michael J. Davies. Protein and peptide alkoxyl radicals can give rise toC-terminal decarboxylation and backbone cleavage [J]. Archives ofbiochemistry and biophysics.1996.336(1):163-172.
[82]文镜，张春华，董雨，等.蛋白质羰基含量与蛋白质氧化损伤[J].食品科学.2003.24(10):153-157.
[83]郑荣梁.自由基生物学[M].北京:高等教育出版社.1992.
[84] Thomas C. Squier. Oxidative stress and protein aggregation during biologicalaging [J]. Experimental Gerontology.2001.(36):1539-1550.
[85]李培峰.活性氧对铜锌超氧化物歧化酶的氧化修饰作用[J].生理科学进展.1995.26(1):50-52.
[86]李培峰，方允中，陈吉中，等.活性氧对蛋白质抗原与其相应抗体反应性增强的效应[J].中国免疫学杂志.1994.10(2):84-86.
[87] Stadtman ER, Levine RL. Free radical-mediated oxidation of free amino acidsand amino acid residues in proteins [J]. Ami-no Acids.2003.25(3-4):207-218.
[88] Stadtman ER. Metal ion-catalyzed oxidation of proteins biochemicalmechanism and biological consequences [J]. Free radicalbiology&Medicine.1990.9:315-325.
[89] Stadtman ER. Oxidation of free aminoacids and aminoacid residues in proteinsby radiolysis and by metal-catalyzed reaction [J]. AnnuRevBiochem.1993.62:797-821.
[90] Earl RStadtman, CNOliver. Metal-catalyzed oxidation of proteins [J]. JBiolChem.1991.266:2005-2008.
[91]文镜，李晶洁，郭豫，等.用蛋白质羰基含量评价抗氧化保健食品的研究[J].中国食品卫生杂志.2002.14(4):13-17.
[92] Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, et al. Advancedoxidation Protein Products as a novel marker of oxidative stress in uremia.Kidney Int.1996.49:1304-1313.
[93] Witko-Sarsat V, Friedlander M, Nguyen Khoa T, et al. Advanced oxidationProtein Products as novel mediators of inflammation and monocyte activationin chronic renal failure. J lmmunol.1998.161:2524-532.
[94] Wilkinson KD. Ubiquitination and deubiquitination: tar-geting of proteins fordegradation by the proteasome. Semin Cell Dev Biol.2000.11:141-148.
[95] Glickman MH, Maytal V. Regulating the26S pro2teasome [J]. Microbiol andImmunol.2002.268(2):43-47.
[96]何洪智，赵晓航，张立勇，等.蛋白质泛素化降解途径与肿瘤发生的关系[J].世界华人消化杂志.2002.10(12):1365-1368.
[97] Glickman MH. Getting in and out of the proteasome [J]. Semin Cell Dev Biol.2000.11(3):149-158.
[98] Martone ME, Jones YZ, Young SJ, Modification of postsynaptic densities aftertransient cerebral ischemia: a quantitative and three-dimensional ultrastructuralstudy. J Neurosci.1999.19:1988-1997.
[99] Hu BR, Martone ME, Jones YZ, et al. Protein aggregation after transientcerebral ischemia. J Neurosci.2000.20:3191-3199.
[100] Hu BR, Janelidze S, Ginsberg MD, et al. Protein aggregation after focal brainischemia and reperfusion. J Cereb Blood Flow Metab.2001.21:865-875.
[101] CN Oliver, AB ong-whan. Age-related changes in oxidized proteins [J]. TheJournal of Biological Chemistry.1987.262:5488-5491.
[102] CD Smith, JM Carney, PE Starke-Reed, et al. Excess brain Protein oxidationand enzyme dysfunction innormal aging and in Alzheimerdisease [J]. MedicalSciences.1991.88:10540-10543.
[103] Richter T, Munch G, Luth HJ, et al. Immunochemical crossreactivity ofantibodies specific for "advanced glycation endproducts" with "advancedlipoxidation endproducts"[J]. Neurobiol Aging.2005.26(4):465-474.
[104] Lyras L, Cairns NJ, Jenner A, et al. An assessment of oxidative damage toproteins, lipids and DNA in brain from patients with Alzheimer's disease [J].JNeurochem.1997.6(85):2061-2069.
[105] Dauer W, Przedborski S. Parkinson’s disease: mech-anisms and models [J].Neuron.2003.39:889-909.
[106] Basso M, Giraudo S, Corpillo D, et al. Proteomea-nalysis of human substantianigra in Parkinson’s dis-ease [J]. Proteomics.2004.4:3943-3952.
[107] Alam ZI, Daniel SE, Lees AJ, et al. Ageneralised in crease in proteincar-bonylsin the brain in Parkinson′s but not incidental Lewy body disease [J].JNeurochem.1997.69(3):1326-1329.
[108] Munch G, Luth HJ, Wong A, et al. Crosslinking of alpha-synuclein byadvanced glycation endproducts-an early pathophysiological step in Lewy bodyformation?[J]. Journal of Chemical Neuroanatomy.2000.20(3-4):253-257.
[109] Morabito F, Cristani M, Saija A, et al. Lipid peroxidation and protein oxidationin patients affected by Hodgkin's lymphoma [J]. Mediators Inflamm.2004.13(5-6):381-383.
[110] Ishii T, Yasuda K, Akatsuka A, et al. A mutation in the SDHC gene of complexII increases oxidative stress resulting in apoptosis and tumorigenesis [J]. CancerRes.2005.65(1):203-209.(15-110为综述文献)
[111] Longa EZ, Weinstein PR, Carlson S,et al. Reversible middle cerebral arteryocclusion without craniectomy in rats[J]. Stroke.1989.20(l):84-91.
[112] Xing BZ，Chen H，Zhang M，et al..Ischemic Post-conditioning protects brainand reduces inflammation in a rat model of focal cerebralischemia/reperfusion. JNeurochem.2008.105(5):1737-1745.
[113] Jolitha AB, Subramanyam MV, Asha Devi S: Modification by vitamin E andexercise of oxidative stress in regions of aging rat brain: studies on superoxidedismutase isoenzymes and protein oxidation status. Exp Gerontol.2006.41:753-763.
[114] Guo JY, Yang T, Sun XG, et al: Ischemic postconditioning attenuates liverwarm ischemia-reperfusion injury through Akt-eNOS-NO-HIF pathway. JBiomed Sci.2011.18:79.
[115] Liu KX, Li YS, Huang WQ, et al: Immediate postconditioning duringreperfusion attenuates intestinal injury. Intensive Care Med.2009.35:933-942.
[116] Zhou C, Tu J, Zhang Q, et al: Delayed ischemic postconditioning protectshippocampal CA1neurons by preserving mitochondrial integrity viaAkt/GSK3β signaling. Neurochem Int.2011.59:749-758.
[117] Prasad SS, Russell M, Nowakowska M: Neuroprotection induced in vitro byischemic preconditioning and postconditioning: modulation of apoptosis andPI3K-Akt pathways. J Mol Neurosci.2011.43:428-442.
[118] Wang Q, Zhang X, Ding Q, et al: Limb remote postconditioning alleviatescerebral reperfusion injury through reactive oxygen species-mediatedinhibition of delta protein kinase C in rats. Anesth Analg.2011.113:1180-1187.
[119] Zhang W, Miao Y, Zhou S, et al: Neuroprotective effects of ischemicpostconditioning on global brain ischemia in rats through upregulation ofhippocampal glutamine synthetase. J Clin Neurosci.2011.18:685-689.
[120] Yuan Y, Guo Q, Ye Z, et al: Ischemic postconditioning protects brain fromischemia/reperfusion injury by attenuating endoplasmic reticulumstress-induced apoptosis through PI3K-Akt pathway. Brain Res.2011.1367:85-93.
[121] Ji X, Luo Y, Ling F, et al: Mild hypothermia diminishes oxidative DNAdamage and pro-death signaling events after cerebral ischemia: a mechanismfor neuroprotection. Front Biosci.2007.12:1737-1747.
[122] Murín R, Drgová A, Kaplán P, et al: Ischemia/Reperfusion-induced oxidativestress causes structural changes of brain membrane proteins and lipids. GenPhysiol Biophys.2001.20:431-438.
[123] Shacter E: Quantification and significance of protein oxidation in biologicalsamples. Drug Metab Rev.2000.32:307-326.
[124] Lehotsky J, Murín R, Strapková A, et al: Time course ofischemia/reperfusion-induced oxidative modification of neural proteins in ratforebrain. Gen Physiol Biophys.2004.23:401-415.
[125] Murotomi K, Takagi N, Takeo S, et al: NADPH oxidase-mediated oxidativedamage to proteins in the postsynaptic density after transient cerebral ischemiaand reperfusion. Mol Cell Neurosci.2011.46:681-688.
[126]18Sugawara T, Chan PH. Reactive oxygen radicals and pathogenesis ofneuronal death after cerebral ischemia. Antioxid Redox Signal.2003.5:597-607.
[46] Zamzami N, Kroemer G. The mitochondrion in apoptosis how Pandoras' boxopens [J]. NatRevMolCell Biol.2001.2(1):67-71.
[47] Joza N, Susin SA, Daugas E, Stanford WL, Cho SK, Li CY, et a l. E s-sentialrole of the mitochondrial apoptosis-inducing factor in pro-grammed cell death[J]. Nature.2001.410(6828):549-554.
[48] Nielsen M, Lambertsen KL, Clausen BH, Meldgaard M, Diemer NH, Zimmer J,et al. Nuclear tran slocation of endonuclease G in de-generating neurons afterpermanentm iddle cerebral artery occlusion in mice [J]. Exp Brain Res.2009.194(1):17-27.
[49] Sugawara T, Noshita N, Lewen A, Gasche Y, Ferrand-Drake M, Fujimura M, etal. Overexpression of copper/zinc superoxide dismutase in transgenic ratsprotects vu lnerable neurons against ischem ic damage by blocking themitochondrial pathway of caspase activation [J]. J Neurosci.2002.22(1):209-217.
[50] Siegelin M, Touzani O, Toutain J, Liston P, Rami A. Induction andredistribution of XAF1, a new antagonist of XIAP in the rat brain after transientfocal ischemia [J]. Neurobiol Dis.2005.20(2):509-518.
[51] Kaufman RJ, Stress signaling from the lumen of the endoplasmic reticulum:coordination of gene transcriptional and translational controls [J].Genes Dev.1999.13(10):1211-1233.
[52] Koumenis C, Wouters BG."Trans lating" tumor hypoxia: un folded proteinresponse (UPR)-dependent and UPR-independent path-ways [J]. Mol CancerRes.2006.4(7):423-436.
[53] Dalton TP, Shertzer HG, Puga A. Regulation of gene expres-sion by reactiveoxygen [J]. Annu Rev Pharmacol Toxicol.1999.39:67-101.
[54] Yu Z, Zhou D, Bruce-Keller AJ, et al. Lack of the p50submit of nuclearfactor-κB increase the vulnerability of hip-pocampal neurons to excitotoxicinjury [J]. J Neurosci.1999.19(20):8856-8865.
[55] Gasche Y, Copin JC, Sugawara T, et al. Matrix metallopro-teinase inhibitionprevents oxidative stress-associated blood-brain barrier disruption aftertransient focal cerebral ischemia [J]. J Cereb Blood Flow Metab.2001.21(12):
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |