三七二醇预处理诱导脑缺血耐受及对GFAP和IL-1 β mRNA表达水平的影响
摘要
目的通过观察三七二醇预处理对局灶性脑缺血大鼠的神经功能、病理学改变,Nissl体变化、脑梗死体积、脑组织中Glibal fibrillary acidic protein(GFAP)、interleukin-1β(IL-1β)mRNA表达水平的影响,探讨三七二醇预处理能否诱导缺血耐受及可能的机制。
方法SD大鼠随机分为空白组、模型组(MCAO)、预缺血+模型组(IPC+MCAO)、三七二醇预处理组(PDS+MCAO)、三七二醇治疗组(MCAO+PDS)、假手术组(SS+SS)6组。空白组不给予任何干预;MCAO组连续3d腹腔注射生理盐水后,给予2h MCAO,再灌注22h后处死动物;IPC给予10min IPC,连续腹腔注射生理盐水3d后再给予2h MCAO,再灌注22h后处死;SS组给予10min SS,3d后给予2h SS,24h后处死动物;PDS+MCAO组给予3d PDS后给予2h MCAO,造模后24h处死;MCAO+PDS组予2h MCAO,再予PDS治疗3d后处死。造模后观察大鼠神经功能缺失情况,HE染色观察病理改变、Nissl染色观察Nissl体、TIC染色检测梗死体积、免疫组化染色观察GFAP阳性表达、RT-PCR检测IL-1βmRNA表达水平。实验数据用SPSS13.0处理,统计用ONE-WAY ANOVA检验。
结果:IPC+MCAO、PDS+MCAO组脑梗死体积表达较MCAO组减少,三组间有统计学差异(p＜0.05)。IPC+MCAO、PDS+MCAO组的尼氏体积分光密度、GFAP表达水平较与MCAO组比较升高,三者间有统计学差异(p＜0.05)。IPC+MCAO、PDS+MCAO组的IL-1βmRNA表达水平与MCAO组比较降低,三者间有统计学差异(p＜0.05)。
结论:PDS预处理诱导了脑缺血耐受,对将要发生的严重脑缺血具有保护作用。星形胶质细胞的活化及抑制炎性反应可能是三七二醇预处理诱导脑缺血耐受重要机制。
Objective:To investigate the influence of Panasadiol Saponins(PDS) preconditioning on the cerebral ischemia in rats and the probable mechanisms,we set up a focal cerebral ischemia model and observe the changes of nerve function, Nissl body,infarct volume,the expression of Glial fibriUary acidic protein(GFAP) and interleukin-1β(IL-1β)mRNA in brain after acute cerebral ischemia.
Method:SD rats randomly divided into six groups:blank,model(NS+ MCAO),ischemic preconditioning(IPC+MCAO),PDS preconditioning(PDS+M CAO),PDS treatment(MCAO+PDS),sham operated(SS+SS).Nonintervention to blank group;after intraperitoneal injection of NS continuously 3 days to mode 1 group,gave 2h MCAO,executed after reperfusion 22h;10 min IPC to IPC group,3 days later,gave 2h MCAO,executed after reperfusion 22h;10min SS to SS group,gave 2h SS after 3 days,executed after 24h;PDS for 3 days t o PDS+MCAO group,gave 2h MCAO,executed after model building 24h.2h MCAO to MCAO+PDS group,executed after PDS treatment for 3 days;obser ving the information of loss of nerve function of rats after model building,pat hological changes of HE dyeing,Nissl body observation of Nissl dyeing,inf arct volume detection of TTC dyeing,observation of GFAP masculine expressi on of immunity tissue chemistry dyeing,detection of IL-1βmRNA express lev el of RT-PCR.Experimental data was dealt with SPSS13.0,tested statistic with ONE-WAY ANOVA.
Result:cerebral infarction volume of IPC+MCAO and PDS+MCAO group are more decreased than MCAO group,there are statistic differences among the three groups(p＜0.05),the IOD of nissl body and GFAP express levels of IPC+MCAO and PDS+MCAO group are higher than MCAO group,there are statistic differences among the three groups(p＜0.05).IL-1βmRNA express levels of IPC+MCAO and PDS+MCAO group are decreased compare with MCAO group,there are statistic differences among the three groups(p＜0.05).
Conclusion:PDS preconditioning may intluce ischemic toleranee in organism, and protects against neuronal damages after subsequent lethal ischemic insults.The activation of Astrocytes and inhibit inflammatory reaction are possibly the important mechanism of PDS preconditioning induced ischemic tolerance.
方法SD大鼠随机分为空白组、模型组(MCAO)、预缺血+模型组(IPC+MCAO)、三七二醇预处理组(PDS+MCAO)、三七二醇治疗组(MCAO+PDS)、假手术组(SS+SS)6组。空白组不给予任何干预;MCAO组连续3d腹腔注射生理盐水后,给予2h MCAO,再灌注22h后处死动物;IPC给予10min IPC,连续腹腔注射生理盐水3d后再给予2h MCAO,再灌注22h后处死;SS组给予10min SS,3d后给予2h SS,24h后处死动物;PDS+MCAO组给予3d PDS后给予2h MCAO,造模后24h处死;MCAO+PDS组予2h MCAO,再予PDS治疗3d后处死。造模后观察大鼠神经功能缺失情况,HE染色观察病理改变、Nissl染色观察Nissl体、TIC染色检测梗死体积、免疫组化染色观察GFAP阳性表达、RT-PCR检测IL-1βmRNA表达水平。实验数据用SPSS13.0处理,统计用ONE-WAY ANOVA检验。
结果:IPC+MCAO、PDS+MCAO组脑梗死体积表达较MCAO组减少,三组间有统计学差异(p＜0.05)。IPC+MCAO、PDS+MCAO组的尼氏体积分光密度、GFAP表达水平较与MCAO组比较升高,三者间有统计学差异(p＜0.05)。IPC+MCAO、PDS+MCAO组的IL-1βmRNA表达水平与MCAO组比较降低,三者间有统计学差异(p＜0.05)。
结论:PDS预处理诱导了脑缺血耐受,对将要发生的严重脑缺血具有保护作用。星形胶质细胞的活化及抑制炎性反应可能是三七二醇预处理诱导脑缺血耐受重要机制。
Objective:To investigate the influence of Panasadiol Saponins(PDS) preconditioning on the cerebral ischemia in rats and the probable mechanisms,we set up a focal cerebral ischemia model and observe the changes of nerve function, Nissl body,infarct volume,the expression of Glial fibriUary acidic protein(GFAP) and interleukin-1β(IL-1β)mRNA in brain after acute cerebral ischemia.
Method:SD rats randomly divided into six groups:blank,model(NS+ MCAO),ischemic preconditioning(IPC+MCAO),PDS preconditioning(PDS+M CAO),PDS treatment(MCAO+PDS),sham operated(SS+SS).Nonintervention to blank group;after intraperitoneal injection of NS continuously 3 days to mode 1 group,gave 2h MCAO,executed after reperfusion 22h;10 min IPC to IPC group,3 days later,gave 2h MCAO,executed after reperfusion 22h;10min SS to SS group,gave 2h SS after 3 days,executed after 24h;PDS for 3 days t o PDS+MCAO group,gave 2h MCAO,executed after model building 24h.2h MCAO to MCAO+PDS group,executed after PDS treatment for 3 days;obser ving the information of loss of nerve function of rats after model building,pat hological changes of HE dyeing,Nissl body observation of Nissl dyeing,inf arct volume detection of TTC dyeing,observation of GFAP masculine expressi on of immunity tissue chemistry dyeing,detection of IL-1βmRNA express lev el of RT-PCR.Experimental data was dealt with SPSS13.0,tested statistic with ONE-WAY ANOVA.
Result:cerebral infarction volume of IPC+MCAO and PDS+MCAO group are more decreased than MCAO group,there are statistic differences among the three groups(p＜0.05),the IOD of nissl body and GFAP express levels of IPC+MCAO and PDS+MCAO group are higher than MCAO group,there are statistic differences among the three groups(p＜0.05).IL-1βmRNA express levels of IPC+MCAO and PDS+MCAO group are decreased compare with MCAO group,there are statistic differences among the three groups(p＜0.05).
Conclusion:PDS preconditioning may intluce ischemic toleranee in organism, and protects against neuronal damages after subsequent lethal ischemic insults.The activation of Astrocytes and inhibit inflammatory reaction are possibly the important mechanism of PDS preconditioning induced ischemic tolerance.
引文
[1]王拥军主编.卒中单元:脑血管病最有效的治疗方法.北京,科学技术文献出版社 2004,1.
[2]Murry CE,Jennings RB,Reimer KA.Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium.[J].Circulation,1986,74(5):1124-1136.
[3]Kitagawak K,Matssumoto M,Tagaya M.et al."Ischemia tolerance" phenomenon found in the Brain[J].Brain Res,1990;58:21-24.
[4]Longa EZ,Weinstein PR,Carson S,et al.Reversible middle cerebral artery occlusion without crainietomy in rats[J].Stroke.1989,20(1):84-91
[5]施新猷编著.现代医学实验动物学.2000.9.485
[6]张成英,殷常荣,王小标等.大鼠脑动脉解剖及其在脑缺血模型中的运用[J]蚌埠医学院学报,1995,20(4):229-230.
[7]张成英,姚家庆,田鹤村等.大鼠脑动脉环的解剖学观察[J].解剖学杂志,1996,19(6):506-508.
[8]Markgraf CG,Kraydieh S,Prado R,et al.Comparative histopathologic consequences of photohrombotic occlusion of the distal middle cerebral artery in Sprague-Dawley and Wistary rats[J].Stork,1993;24(2):286-292
[9]Cai H,Yao H,Setsuro,et al.Photothrombotic middle cerebral artery occlusion in spontaneously hypertensive rats:Influence of substrain,gender and distal middle cerebral artery patterns on infarct size[J].Stroke,1998,29(10):1982-1987.
[10]Wang CX,Yang Yang T,et al.A focal embolic modle of cerebral ischemia in rats:introduction and evaluation[J].Brain Res Protoc,2001,7(2):11:5-20
[11]Tamma A,Graham DI,Mcculloch J,et al.Focal cerebral ischemia in the rat.[J].Cereb Blood Flow Metab,1981,1(1):53-60
[12]Diet rich WD,Nakeyamam H,Watson BD,Morphological consequences of early reperfusion following thrombotic or mechanical occlusion of the rat middle cerebral artery[J].Acta Neruopathol,1989,78(6):605-14
[13]王新志等编著.中风脑病诊疗全书.北京.中国医药科技出版社,2000.1.
[14]鲍建才,刘刚,从登立等.三七的化学成分研究进展[J]中成药,2006,(2)28,2:246-253.
[15]刘建辉,翼凤云,王婷等.三七总皂甙对实验性脑缺血脑血流及血脑屏障的影响作用[J].河北医学,2002,24(4):249.
[16]史以菊,吴俊芳,夏作理等.三七总皂甙对大鼠局灶性脑缺血的保护作用[J].中国临床药理学与治疗学,1999,4(4):272.
[17]史以菊,王曙光,卢连元等.三七皂甙单体Rb1、Rg1对局灶性脑缺血运动功能及体感诱发电位的影响[J].现代康复,2001,5(10):52.
[18]开丽,王中峰,萧家思.人参二醇组皂甙对正常和“缺血”诱导的大鼠大脑皮层神经元L-型钙通道的影响[J]第三军医大学学报,1997,4:115-118.
[19]G.w.Tyson et al.Cerebrovascular permeablily following MCA occlusion in the rat[J].J Neurosury,1982,54:186.
[20]卞留贯张天锡赵卫国脑缺血后脑细胞线粒体LPO、SOD变化[J].中国神经精神疾病杂志,1994,20:27.
[21]卞留贯,张天锡,赵卫国.EAA与自由基在致脑缺血脑损害中的相互关系[J].国外医学脑血管分册,1994,2:139.
[22]卞留贯,张天锡,赵卫国.ET与自由基在脑缺血中的相互作用[J].中风与神经疾病杂志,1993,10:203.
[23]卞留贯,张天锡,赵卫国.局灶脑缺血后脑LPO、SOD变化[J]上海二医大学报,1993,13:262.
[24]卞留贯,张天锡,赵卫国.Ca~(2+)与自由基在脑缺血时相互作用[J]中华实验外科杂志,1994,11:190.
[25]鞠躬编著.神经生物学:北京:人民卫生出版社,2004.5:47
[26]Masters CL,Simms G,Weinman NA.et al.Proc Nail Acad Sci,1985,82:4245-4249.
[27]Hardy J,Selkoe DJ.et al.Science,2002,297:353-356.
[28]Joseph JA,Shukitt HB,Denisova NA.et al.Neurobiol Aging,2001,22:161-163.
[29]W.Dalton Dietrich,Gary Danton,Aviva C.Hopkins,et al.Thromboembolic Events Predispose the Brain to Widespread Cerebral Infarction After Delayed Transient Global Ischemia in Rats[J].Stork,1999,30(4):855-861
[30]Shama G,Vijayaraghavan S Nicotinic cholinergic signaling in hippocampal astrocytes involves calcium-induced calcium release from intracellular stores[J].Proc Natl Sci USA,2001,98(7):4148-53.
[31]Louw DF,Masada T,Suthertand GRAD.Ischemia neuronal injury is ameliorated by astrocyte activation[J].Can J Neurol Sci.1998.25(2):102-107
[32]Nawashim H,Brenner M,Fukui S,et al.High susceptibility to ischemia in GFAP-null mice[J].J Cereb Blood Flow Metab.2000,20(7):1040-1044.
[33]王春辉,高明,韩雪梅等.大鼠脑缺氧预处理及局灶性脑缺血后GFAP表达的变化及意义.[J].中国实验诊断学.2005,12(9)6:884-886
[34]周俊英,刘小利,罗祖明.三七三醇皂甙增进大鼠脑缺血耐受的作用及对GFAP和bFGF 表达的影响[J].华西药学杂志.2005,20(6):489-492
[35]Sugawara T,Noshita N,Lewen A,et ai.Neuronal Expression of the DNA Repair Protein KU 70 After Ischemia Preconditioning Corresponds to Tolerance to Global Cerebral Ischemia[J].Stork,2001,32(10):2388-2393
[36]Shamloo M,Wieloch T,.Changes in protein tyrosin phosphorylation in the rat brain after cerebral ischemia in a model of ischemia tolerance[J].J Cereb Blood Flow Metab,1999,19(2):173
[37]Bernaudin M,Nedelec A,Divoux D,et al.Nomobaric hypoxia induces tolerance to focal permanent cerebral ischemia in association with an increased expression of hypoxia inducible factor 1 and its target genes,Erythropoietin and VEGF,in the adult mouse brain[J].J Cereb Blood Flow Metab,2002,22(4):393
[38]BONNI A,SUN Y,VICENS MN,et al.Regulation of Gliogenesis in the Central Nervous System by the JAK-STAT Signaling Pathway[J].Science(S0036-8075),1997,278(17):477-483
[39]RAJANP P,RONALD DG,Multiple Routes to Astrocytic Differentiation in the CNS[J].J Neurosci(S0020-7454),1998,18(10):3620-3629
[38]Rothwel NJ.Functions and mechanisms of interleukin 1 in the brain[J].Trends Phamacol Sci.1991,12(11):430-436
[39]Wang X,Yue TL,Barone FC,et al.Concomitant cortical expression of TNF-a and IL-Iβ mRNAs follows early response gene expression in transient focal ischemia[J].Mol Chem Neuropathol.1994,23(2-3):103-114
[40]Loddick SA,Rothwell NJ.Mechanisms of tumor necrosis factor alpha action on neurodegeneration interaction with insulin-like growth factor-1[J].Proc Natl Acad Sci USA,1999,96(17):9449-9451.
[41]Rothwell NJ,Luheshi G,et al.Pharmacology of interleukin-1 actions in the brian[J].Adv Pharmacol,1994,25(6):1-20
[42]Hallenbeck JM,Dutka AJ,Kochanek PM,et al.Stroke risk factor prepare rat brain stem tissue for midified local Shwartzman reaction.[J].Stroke,1988,19:863
[43]Liu T,Dornel PC,Young PR,et al.IL-1βmRNA expression in ischemia rat cortex.[J]Stroke,1993,24(11):1746-1764.
[44]Sharma BK,Kumar K.Role of proinflammatory eytokins in cerebral isehemia[J]Metab Brain Dis,1998,13:1-8
[45]HILLOUSE E W,KIDA S,IANNOTFI F.Middle cerebral artery occlusion in the rat causes a biphasie production of immunoreactive interleukin-1β in the cerebral cortex[J].Neurosic Lett,1998,249:177-19
[46]WieBner C,Gehrmann J,Lindholm D,et al.Expression of transforming growth factor-β1 and interleukin-1β mRNA in rat brain following transient forebrain ischemia[J]Acta Neurlpathol,1993,86:439-446
[47]M Buttini A,Sauter HWG M.Bpddeke,et al.Induction of interleukin-1β mRNA after focal cerebral ischemia in the rat[J]Mol Brain Res,1994,23:126-134
[48]杜柏岩,关秀茹,高光强等.IL-1β对大鼠脑缺血再灌注损伤的意义[J]哈尔滨医科大学学报,2000(4)34,2:124-125
[49]周红,乔健.大鼠局灶性脑缺血再灌注纹状体内肿瘤坏死因子-α及白细胞介素-1β的动态变化[J]现代医学,2005,33(5),5:294-296
[50]Yamasaki Y,Metsuura N,Shozuhara H.et al.Interleukin-1 as a pathogenetic mediator of ischemic brain damage in rats.[J]Stroke,1995,26(4):676-680
[51]Wang X,Barone FC,Aiyar NV.et al.Interleuldn-1 receptor and receptor antagonist gene expression after focal stroke in rats[J]Stroke,1997,28(1):155-161
[52]Relton JK,Martin D,Thompson Re,et al.Peripheral administration of interleukin 1 receptor antagonist inhibits brain damage after focal cerebral ischemia in the rat.[J]Exp Neural,1996,138(2):206-13
[53]Hara H,Friedlander RM,Gagliaardini V,et al.Inhibition of interleukin 1 beta convening enzyme family proteases reduces ischemic and excitotoxie neuronol damage.[J]Proc Natl Acad Sci USA,1997,94(5):2007-2012
[54]Loddick SA,Mackenzie A,Rothwell NJ,et al.An ICE inhibitor Z-VAD-DCB attenuates ischemie brain damage in the rat[J]Neuroreport,1996,7(9):1465-1468
[55]STROEMER R P,ROTHWELL NT.Ortical protection by localized striatal injection of IL-1following cerebral ischemia in the rat[J].J Cereb Blood Flow Metab,1997,17:597-604
[56]王涛,陈莉,文亮.YVAD-FMK对大鼠全脑缺血再灌注后神经元损伤的影响[J]中国急救医学,2001,21(2),2:63-65
[57]李旦,孙桂莲,史金阳等.白细胞介素1β多克隆抗体对新生大鼠缺氧缺血性脑损伤的作用[J]卒中与神经疾病,1996,6,1:7-8
[58]王知秋,陈城,杨国源等.MEK抑制剂小鼠脑缺血后ERK通路的激活和IL-1β mRNA合成[J]复旦学报(医学版):2004,31(2):119-123
[1]Murry CE,Jennings RB,Reimer KA.Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium.Circulation,1986,74(5):1124-1136.
[2]Kitagawak K,Matssumoto M,Tagaya M.et al."Ischemia tolerance" phenomenon found in the Brain[J].Brain Res,1990;58:21-24.
[3]Monkayo J,de Freitas GR,Bogousslavsky J.et al.Do transient ischemic attacks have a neuroprotective effect? Neurology,2000,54(11):2089-2094.
[4]Kitagawa K,Matsumoto M,Kuwabara K.et al."Ischemia tolerance" phenomenon detected in various brain regions.Brain Res,1991,561:203-211.
[5]Glazier SS,O'Rourke DM,Graham DI.et al.Induction of ischemic tolerance following brief focal ischemia in rat brain.J Cereb Blood Flow Metab.1994,14:545-553.
[6]Miyashida K,Abe H,Nakajima T.Induction of ischemia tolerance in gerbil hippocampus by pretreatment with focal ischemia.Neuroreport.1994,6:46-48.
[7]Simon RP,Niiro M,Gwinn R.Prior ischemia stress protect against experimental stroke.Neurosci.Lett,1993,163:135-137.
[8]Barone FC,White RF,Spera PA.et al.Ischemia preconditioning and brain tolerance.Temporal histological and function outcomes,protein synthesis requirement,and interlukin-1 receptor antagonist and early gene expression.Stroke.1998,29:1937-1951.
[9]Masada T,Hua Y,Xi G.et al.Attenuation of ischemia brain edema and cerebrovascular injury after ischemia preconditioning in the rat.J Cereb Blood Flow Metab,2001,21(1):22-33
[10]Zhao HG,Li WB,LIQJ.et al.Limb ischemic preconditioning attenuates apotosis of pyramidal neurons in the CA1 hippocampus induced by cerebral ischemia-reperfusion in rats.Acta Physiologica Sinica,2004,56(3):407-412.
[11]Dawson DA,Furuya K,Gotoh J.et al.Cerebrovascular hemodynamics and ischemic tolerance:lipopolysaccharide-induced resistance to focal cerebral ischemia is not due to change in severity of the initial ischemia insult,but is associated with preservation of microvascular perfusion.J Cereb Blood Flow Metab,1999,19:1229-1237.
[12]Nawashiro H,Tasakik,Ruetzler CA.et al.TNF-alpha pretreatment induces protective effects against focal cerebral ischemia in mice.J Cereb Blood Flow Metab,1997,17(5):483-490.
[13]Masada T,Xi G,Hua Y.et al.The effects of thrombin preconditioning on focal cerebral ischemia in rats.Brain Res,2000,867(1-2):173-179.
[14]Toyoda T,Kassell NF,Lee KS.Induction of tolerance against ischemia reperfusion injury in the rat brain by preconditioning with the endotoxin analog diphosphoryl lipid A.J Neurosurg,2000,92:435-441.
[15]向强,文亮,高强国.内毒素预处理对大实权脑缺血/再灌注后炎性反应影响的实验研究.第三军医大学学报,2006,28(7):694-696.
[16]Lauritzen I,De Weille JR,Lazdunski M.The potassium channel openercromakalim prevents glutamate-induced cell death in hippocampal neurons.J Neurochem,1997,69:1570-1579.
[17]Shimizu K,Lacza Z,Rajapakse N.et al.MitoK(ATP) opener,diazoxide reduces neuronal damage after middle cerebral artery occlusion in the rat.Am J Physiol Heart Circ Physiol,2002,283:H1005-1011.
[18]Blondeau N,Plamondon H,Richelme C.et al.K(ATP) channel openers,adenosine agonists and epileptic preconditioning are stress signals inducing hippocampal neuroprotection.Neuroscience,2000,100:465-474.
[19]胡明,刘昌勤,冯作化.尼莫地平预处理和梗塞后治疗对大鼠脑缺血损伤保护作用的比较研究.脑与神经疾病杂志,2005,13(3)182-185.
[20]邬伟东,柴滢,王屹等.尼卡地平预处理大鼠脑缺血后神经细胞凋亡及其调控基因bcl-2的表达.中华创伤杂志,2005,(6),21,6:459-460.
[21]Lysko PG,Webb CL,Yue JL.et al.Neuroprotective effects of tetrodotoxin as a Na~+ channel modulator and glutamate release inhibitor in cultured rat cerebrallar neurons and in gerbil global brain ischemis.Stroke,1994,25(12):2476-2478.
[22]Grilli M,Pizzi M,Memo M.et al.Neuroprotection by aspirin and sodium salicylate through blockade of NF-κB activation.Science,1996,274(5291):1383-1385.
[23]Khayyam N,Thavendiranathan P,Carmichael FJ.et al.Neuroproetective effects of acetylsalicylic acid in animal model of focal brain ischemia.Neuroreport,1999,10(2):371-374.
[24]孙风云,闵连秋.阿司匹林预处理对局灶性脑缺血大鼠超氧化物歧化酶及丙二醛的影响.中国临床康复,2006,(10),30:162-163.
[25]罗祖明,郝玉曼.奥扎格雷钠对大鼠脑缺血耐受作用及核因子-κB表达的影响.中华老年医学杂志,2005,(2),24,2:134-136.
[26]Wise-Faberowski L,Raizada MK,Summners C.Oxygen and glucose deprivation-induced neuronal apoptosis is attenuated by haothane and isoflurane.Anesth Analg,2001,93:1281-1287.
[27]Kurth CD,Priestley M,Watzman HM.et al.Desflurane confers neurologic protection for deep hypothemic circulatory arrest in newborn pigs.Anesthesiology,2001,95:959-964.
[28]Kapinya KJ,Prass K,Dimagl U.Is flurane induced prolonged protection against cerebral ischemia in mice:a redox sensitive mechanism?Neuroreport,2002,13:1431-1435.
[29]吴明春,熊利泽,朱正华等.异氟醚预处理对脑保护作用的剂量-效应关系.第四军医大学学报,2002,23:1357-1359.
[30]Bhardwaj A,Alejandro F,Alkayed NJ.et al.Anesthetic choice of halo thane versus propofol:impact on experimental perioperative stroke.Stroke,2001,32(8):1920-1925.
[31]Kato H,Kogure K,Araki T.et al.Astroglial and nucroglial reactions in the gerbil hippocampus with induced ischemic tolerance.Brain Res,1994,664(1-2):69-76.
[32]Kobayashi S,Harris VA,Welsh FA.Spreading depression induces tolerance of cortical neurons to ischemia in rat brain.J Cereb Blood Flow Metab.1995,15:721-727.
[33]Otori T,Greenberg JH,Welsh FA.Cortical spreading depression causes a long-lasting decrease in cerebral blood flow and induces tolerance to permanent focal ischemia in rat brain.J Cereb Blood Flow Metab.2003,23:43-45.
[34]Yanamoto H,Hashimoto N,Nagata I.et al.Infarct infarct tolerance against temporary focal ischemia following spreading depression in rat brain.Brain Res,1998,784(1-2):239-49.
[35]胡学斌,赵洪洋,冯哲等.皮层扩散性抑制预处理对大鼠脑缺血性损伤的保护作用.中华实验外科杂志,2006,(8),23,8:968-970.
[36]Nishio S,Yunoki M,Chen ZF.et al.Is-chemic tolerance in the rat neocortex following hypothermic preconditioning.J Neurosurg,2000,93(5):845-851.
[37]Xu H,Aibiki M,Nagoya J.Neuroprotective effect of hyperthermic preconditioning on infracted volume after middle cerebral artery occlusion in rats:role of adenosine receptors.Crit Care Med,2002,30(5):1126-1130.
[38]Uno H,Kobayashi H,Handa Y.et al.Alterations of calciumcal modulin dependent protein kinase Ⅱ activity in ischemia induced neuronal death and neuronal protection against ischemia in the gerbil hippocampus.Acta Neurochir,1999,141:287-294.
[39]Mu D,Chang YS,Vexler ZS.et al.Hypoxia-inducible factor 1 alpha and erythropoietin upregulation with deferoxamine salvage after neonatal stroke.Exp Neurol,2005,195(2):407-415.
[40]Prass K,W jegand F,Schumann P.et al.Hyperbaric oxygenation induced tolerance against focal cerebral ischemia in mice is strain dependent.Brain Res,2000,87(1):146-150.
[41]Aketa S,Nakase H,Kamada Y.et al.Chemical preconditioning with 3-nitropropionic acid in gebil hippocampal Slicea the-apeutic window and the participation of adenosine receptor.Exp Neurol,2000,166(2):385-391.
[42]Xiong L,Zhu Z,Dong H.et al.Hyperbaric oxygen preconditioning induces neuroprotection against ischemia in transient not permanent middle cerebral artery rat model.Chin Med J.2000,113(9):836-9.
[43]Wardsa J.Neuroprotective role of adenosine in the CNS.Pol J Pharmacol,2002,54:313-326.
[44]Simon RP,Cho H,Gwinn R.et al.The temporal profile of 72-kDa heat-shock protein exprcssion foUowing global ischemia.J Neurosci,1991,11(4):881-889.
[45]Currie RW,Ellison JA,White RF.et al.Benign focal ischemic preconditioning induce neuronal hes70 and prolonged astrogliosis with expression of hsp72.Brain Res,2000,863(1-2):169-181.
[46]Kitagawa K,Matsumoto M,Kuwabara K.et al.Ischemic tolerance phenomenon detected in various brain regions.Brain Res,1991,561(2):203-211.
[47]Chen J,Graham SH,Zhu RL.Stress protein and tolerance to focal cerebral ischemia.J Cereb Blood Flow Metab,1996,16(4):566-567.
[48]Vass K,Welch NJ,Nowak TS Jr.et al.Localization of 70-Kda stress protein induction in gerbil after ischemia.Acta Neuropathol Berl,1998:77:128.
[49]Kirino T.et al.J Cereb Blood Flow Metab,1991;11(2):299.
[50]Kane DJ,Ord T,Anton R.et al.Expression of bcl-2 inhibits necrotic neural cell death.J neurosci Res,1995,40(2):269-275.
[51]Kobayashi S,Harris VA,Welsh FA.Spreading depression indueces tolerance of conical neurons to ischcmia in rat brain.J Cereb Blood Flow Metab,1995,15(4):721-727.
[52]Pringle AK,Thomas SJ,Signorelli F.et al.Ischemic pre-conditioning in organotygic hippocampal slice cultures in inversely correlated to the induction of the 72-Kda heat shock protein(HSP72). Brain Res,1999,845(2):152-164.
[53]Douen AG,Akiyama K,Hogan MJ.et al. preconditioning with cortical spreading depressing decrease intraischemic cerebral glutamate levels and down-regulates excitatory amino acid transporters EAAT1 and EAAT2 from rat cerebral cortex plasma membranes. J Neurochem, 2000,75:812-818.
[54]Crabb MC, Choi DW. Ischeraic tolerance in murine cortical cell culture: critical role for NMDA receptors. J Neurosci, 1999,19:1657-1662.
[55]Alsbo CW, Wrang ML, Nielsen M. et al. Ischemic tolerance affects the adenylation state of GluR2 Mrna. Neuroreport,2000,11:3279-3282.
[56]Vanux DL,Strasser A. The molecular biology If apoptosis. Proc Natl Acad Sci USA.1996,193:2239-2244.
[57]Shimizu S,Eguchi Y.Kosaka H. et al. Prevention of hypoxia induced cell death by bcl-2 and bcl-x. Nature. 1995,374:811-813.
[58]Chen J,Graham SH,Nakayama M. et al. Apoptosis repressor genes bcl-2 and bcl-x are expressed in the rat brain following global ischemia. J Cereb Blood Row Metab.1997,17:2-10.
[59]Shimazki K,Ishida A,Kawai N. Increase in bcl-2 oncoprotein and the tolerance to ischemia-induced neuronal death in the geril hippocampus. Neurosci Res.l994,20(l):95-99.
[60]Oltvai ZN,Milliman CL,Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell, 1993;74(4):609-19.
[61]Oltvai ZN,Millman CL,Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, bax that accelerates programmed cell death. Cell. 1993,74:609-619.
[62]Tomasevic G,Sham loo,Istaeli D.et al.Activation of p53 and its target p21 (W AF1/C ipl) and PAG608/W jg-1 in ischemic preconditioning Brain Res Mol Brain Res,1999,70(2):304-313.Expression of BCL-2 inhibibits necrotic neural cell.death.
[63]Zhang RZ,Wu, C,Fujihara H. et al. Both acspase-dependent and caspase-independent pathways may be involved in hippocampal CA1 neuronal death because of loss of cytochrome c From mitochondria in a rat forebrain ischemia model. J Cereb Blood Flow Metab,2001;21(5):529-40.
[64]Liu J,Ginis I,Spatz M. et al. Hypoxic preconditioning protects cultured neurons against hypoxic stress via TNF-alpha and ceramide. Am J Physiol Cell Physiol.2000,278(l):C144-53.
[65]Shamloo M, Rytter A, Wieloch T. Activation pf the extracellular signal-regulated protein kinase cascade in the hippocmpal CA1 region in a rat model of global cerebral ischemic preconditioning. Neuroscience. 1999, 93(1) :81-8
[66]Gonzale-Zuleeta M,Peldman AB,Klesse LJ. et al. Requirement for nitric oxide activation of 21ras/extracellular regulated kinase in near ronal ischemic preconditioning. Proc. Natl Acad Sci USA,2000,97(1):436-441.
[67]Toyoda T,Kassell NF,lee KS. et al. Induction of ischemic tolerance and antioxidant activity by brief focal ischemia. Neuro Report,1997,8(4):847-851.
[68]Lascola C,Kraig RP.et al. Astroglial acid-basedynamics in hyperglycemic and normoglyceic global ischemia. Neurosci Biobehav Rev,1997,21:143-50.
[69]Schurr A,Payne RS,Miller JJ.et al. Glia are the main source of lactate utilized bu neurons for recovery of function posthypoxia.. Brain Res,1997,74,221-4.
[70]Kato H,Kogure K,Araki T. et al. AS troliat and microglial reactions in the gerbil hippocampus with induced ischemic tolerance.Brain Res,1994,664:69-76.
[71]Liu J,Bartels M,Lu A.et al.Microglia/macrophages prolife rate in striatum and neocortex but not in hippocampus after brief global ischemia that produces ischemie tolerance in gerbil brain.J Cereb Blood Flow Metab,2001,21(4):361-73.
[72]Nakata N,Kato H,Kogure K.Effects of repeated cerebral ischemia on extracellular amino acid concentrations measured with intracerebral microdialysis in the gerbil hippocampus.Stroke,1993(3),24:458-464.
[73]Barone FC,White RF,Spera PA.et al.Ischernie preconditioning and brain tolerance:temporal histological and functional outcome,protein synthesis requirement,and inteleukin-1 receptor anatagonist and early gene expression.Stroke,1998,29(9):1937-1951.
[74]Belayev I,Ginsberg MD,Alonso OF.et al.Bilateral isehemie tolerance of rat hippocampus induced by prior unilateral focal ischemia:relationship to c-fos Mrna expression.Neuroreport:1996,8(1):55-59.
[75]Gonzale-Zuleeta M,Peldman AB,Klesse LJ.et al.Requirement for nitric oxide activation of 21ras/extracellular regulated kinase in near renal ischemie preconditioning.Proc.Natl Acad Sci USA,2000,97(1):436-441.
[76]Whitefield PC,Williams R,Pickard JD.et al.Delayed induction of JunB precedes CA_1neuronal death after global ischernia in the gerbil.Brain Res.1999;818(2):450-458.
[77]Okimura Y,Tanno H,Fukduda K.et al.Reactive astrocytes in acute stage after experimental brain injury:relationship to extravasated plasma protein and expression of heat shock protein.J Neurotrauma,1996;13(7):385-393.
[78]Chen D,minami M,Henshall DC.et al...U pregulation of mitoehoir drial base-ezeision repair capability within rat brain brief ischemia.J Cereb Blood Flow Metab,2003,23:88-98.
[79]Iwai M,Hayashi T,Zhang WR.et al.Induction of highly polysialylated neural cell adhesion molecule(PSA-NCAM) in postischemie gerbil hippocampus mainly dissociated with neural stern cell proliferation.Brain Res,2001,902(2):288-293.
[80]Jin K,Minami M,Lan JQ.et al.Neurogenesis in dentate subgranular zone and rostral subventriculture zone after focal cerebral isehemia in the rat.Proc.Natl Acad Sci USA.2001,98:4710-4715.
[81]鄢文海,陈正跃,崔景彬等.β淀粉样蛋白诱导胚胎大鼠神经干细胞凋亡.实用儿科临床杂志,2004,19(8):658-659.
[82]Teacher AB,Yamashima T,Zhao L.et al.Proliferation of neural and neuronal progenitors after global brain isehemia in yong adult macaque monkeys.Mal Cell Neurosci,2003,23(2):292-301.
[83]Arvidsson A,Kokaia Z,Lindvall O.N-methyl-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke.Eur J Neurosci,2001,14(1):10-18.
[84]Orendacova J,Racekova E,Kucharova K.et al.Ependyma as a possible morphological basis of ischemic preconditioning tolerance in rat spinal cord ischemia model:nestin and Fluoro-Jade B observation.Cell Mal Neurobiol,2004,24(3):477-489.
[85]Chimon GN,Wong PT.Ischemie tolerance and lipid peroxidation in the brain.Neuroreport,1998,9(10):2268-2272.
[86]Toyoda T,Kassell NF,Lee KS.Induction of ischemic tolerance and antioxidant activity by brief of focal ischemia.Neuroreport,1997,8(4):847-851.
[87]Mori T,Muramatsu H,Matsui T.et al.Possible role of the superoxide anion in the development of neuronal tolerance following ischemie preconditioning in rats.Neuropathol Appl Neurobiol,2000,26(1):31-40.
[88]Honthius DJ,steward O.Induction of cortical spreading depression with potassium chloride upregulatcs levels of messenger RNA for glial fibrillary acidic protein in cortex and hippocampaus:inhibition by MK-801.Brain Res.1993:618:83-94.
[89]Katayama Y,Muramatsu H,Kamuya T.et al.Ischemic tolerance phenomenon from an approach of energy metabolism and the mitochondrial enzyme activity of pyruvate dehydrogenase in gerbil.Brain Res,1997,746:126-132.
[2]Murry CE,Jennings RB,Reimer KA.Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium.[J].Circulation,1986,74(5):1124-1136.
[3]Kitagawak K,Matssumoto M,Tagaya M.et al."Ischemia tolerance" phenomenon found in the Brain[J].Brain Res,1990;58:21-24.
[4]Longa EZ,Weinstein PR,Carson S,et al.Reversible middle cerebral artery occlusion without crainietomy in rats[J].Stroke.1989,20(1):84-91
[5]施新猷编著.现代医学实验动物学.2000.9.485
[6]张成英,殷常荣,王小标等.大鼠脑动脉解剖及其在脑缺血模型中的运用[J]蚌埠医学院学报,1995,20(4):229-230.
[7]张成英,姚家庆,田鹤村等.大鼠脑动脉环的解剖学观察[J].解剖学杂志,1996,19(6):506-508.
[8]Markgraf CG,Kraydieh S,Prado R,et al.Comparative histopathologic consequences of photohrombotic occlusion of the distal middle cerebral artery in Sprague-Dawley and Wistary rats[J].Stork,1993;24(2):286-292
[9]Cai H,Yao H,Setsuro,et al.Photothrombotic middle cerebral artery occlusion in spontaneously hypertensive rats:Influence of substrain,gender and distal middle cerebral artery patterns on infarct size[J].Stroke,1998,29(10):1982-1987.
[10]Wang CX,Yang Yang T,et al.A focal embolic modle of cerebral ischemia in rats:introduction and evaluation[J].Brain Res Protoc,2001,7(2):11:5-20
[11]Tamma A,Graham DI,Mcculloch J,et al.Focal cerebral ischemia in the rat.[J].Cereb Blood Flow Metab,1981,1(1):53-60
[12]Diet rich WD,Nakeyamam H,Watson BD,Morphological consequences of early reperfusion following thrombotic or mechanical occlusion of the rat middle cerebral artery[J].Acta Neruopathol,1989,78(6):605-14
[13]王新志等编著.中风脑病诊疗全书.北京.中国医药科技出版社,2000.1.
[14]鲍建才,刘刚,从登立等.三七的化学成分研究进展[J]中成药,2006,(2)28,2:246-253.
[15]刘建辉,翼凤云,王婷等.三七总皂甙对实验性脑缺血脑血流及血脑屏障的影响作用[J].河北医学,2002,24(4):249.
[16]史以菊,吴俊芳,夏作理等.三七总皂甙对大鼠局灶性脑缺血的保护作用[J].中国临床药理学与治疗学,1999,4(4):272.
[17]史以菊,王曙光,卢连元等.三七皂甙单体Rb1、Rg1对局灶性脑缺血运动功能及体感诱发电位的影响[J].现代康复,2001,5(10):52.
[18]开丽,王中峰,萧家思.人参二醇组皂甙对正常和“缺血”诱导的大鼠大脑皮层神经元L-型钙通道的影响[J]第三军医大学学报,1997,4:115-118.
[19]G.w.Tyson et al.Cerebrovascular permeablily following MCA occlusion in the rat[J].J Neurosury,1982,54:186.
[20]卞留贯张天锡赵卫国脑缺血后脑细胞线粒体LPO、SOD变化[J].中国神经精神疾病杂志,1994,20:27.
[21]卞留贯,张天锡,赵卫国.EAA与自由基在致脑缺血脑损害中的相互关系[J].国外医学脑血管分册,1994,2:139.
[22]卞留贯,张天锡,赵卫国.ET与自由基在脑缺血中的相互作用[J].中风与神经疾病杂志,1993,10:203.
[23]卞留贯,张天锡,赵卫国.局灶脑缺血后脑LPO、SOD变化[J]上海二医大学报,1993,13:262.
[24]卞留贯,张天锡,赵卫国.Ca~(2+)与自由基在脑缺血时相互作用[J]中华实验外科杂志,1994,11:190.
[25]鞠躬编著.神经生物学:北京:人民卫生出版社,2004.5:47
[26]Masters CL,Simms G,Weinman NA.et al.Proc Nail Acad Sci,1985,82:4245-4249.
[27]Hardy J,Selkoe DJ.et al.Science,2002,297:353-356.
[28]Joseph JA,Shukitt HB,Denisova NA.et al.Neurobiol Aging,2001,22:161-163.
[29]W.Dalton Dietrich,Gary Danton,Aviva C.Hopkins,et al.Thromboembolic Events Predispose the Brain to Widespread Cerebral Infarction After Delayed Transient Global Ischemia in Rats[J].Stork,1999,30(4):855-861
[30]Shama G,Vijayaraghavan S Nicotinic cholinergic signaling in hippocampal astrocytes involves calcium-induced calcium release from intracellular stores[J].Proc Natl Sci USA,2001,98(7):4148-53.
[31]Louw DF,Masada T,Suthertand GRAD.Ischemia neuronal injury is ameliorated by astrocyte activation[J].Can J Neurol Sci.1998.25(2):102-107
[32]Nawashim H,Brenner M,Fukui S,et al.High susceptibility to ischemia in GFAP-null mice[J].J Cereb Blood Flow Metab.2000,20(7):1040-1044.
[33]王春辉,高明,韩雪梅等.大鼠脑缺氧预处理及局灶性脑缺血后GFAP表达的变化及意义.[J].中国实验诊断学.2005,12(9)6:884-886
[34]周俊英,刘小利,罗祖明.三七三醇皂甙增进大鼠脑缺血耐受的作用及对GFAP和bFGF 表达的影响[J].华西药学杂志.2005,20(6):489-492
[35]Sugawara T,Noshita N,Lewen A,et ai.Neuronal Expression of the DNA Repair Protein KU 70 After Ischemia Preconditioning Corresponds to Tolerance to Global Cerebral Ischemia[J].Stork,2001,32(10):2388-2393
[36]Shamloo M,Wieloch T,.Changes in protein tyrosin phosphorylation in the rat brain after cerebral ischemia in a model of ischemia tolerance[J].J Cereb Blood Flow Metab,1999,19(2):173
[37]Bernaudin M,Nedelec A,Divoux D,et al.Nomobaric hypoxia induces tolerance to focal permanent cerebral ischemia in association with an increased expression of hypoxia inducible factor 1 and its target genes,Erythropoietin and VEGF,in the adult mouse brain[J].J Cereb Blood Flow Metab,2002,22(4):393
[38]BONNI A,SUN Y,VICENS MN,et al.Regulation of Gliogenesis in the Central Nervous System by the JAK-STAT Signaling Pathway[J].Science(S0036-8075),1997,278(17):477-483
[39]RAJANP P,RONALD DG,Multiple Routes to Astrocytic Differentiation in the CNS[J].J Neurosci(S0020-7454),1998,18(10):3620-3629
[38]Rothwel NJ.Functions and mechanisms of interleukin 1 in the brain[J].Trends Phamacol Sci.1991,12(11):430-436
[39]Wang X,Yue TL,Barone FC,et al.Concomitant cortical expression of TNF-a and IL-Iβ mRNAs follows early response gene expression in transient focal ischemia[J].Mol Chem Neuropathol.1994,23(2-3):103-114
[40]Loddick SA,Rothwell NJ.Mechanisms of tumor necrosis factor alpha action on neurodegeneration interaction with insulin-like growth factor-1[J].Proc Natl Acad Sci USA,1999,96(17):9449-9451.
[41]Rothwell NJ,Luheshi G,et al.Pharmacology of interleukin-1 actions in the brian[J].Adv Pharmacol,1994,25(6):1-20
[42]Hallenbeck JM,Dutka AJ,Kochanek PM,et al.Stroke risk factor prepare rat brain stem tissue for midified local Shwartzman reaction.[J].Stroke,1988,19:863
[43]Liu T,Dornel PC,Young PR,et al.IL-1βmRNA expression in ischemia rat cortex.[J]Stroke,1993,24(11):1746-1764.
[44]Sharma BK,Kumar K.Role of proinflammatory eytokins in cerebral isehemia[J]Metab Brain Dis,1998,13:1-8
[45]HILLOUSE E W,KIDA S,IANNOTFI F.Middle cerebral artery occlusion in the rat causes a biphasie production of immunoreactive interleukin-1β in the cerebral cortex[J].Neurosic Lett,1998,249:177-19
[46]WieBner C,Gehrmann J,Lindholm D,et al.Expression of transforming growth factor-β1 and interleukin-1β mRNA in rat brain following transient forebrain ischemia[J]Acta Neurlpathol,1993,86:439-446
[47]M Buttini A,Sauter HWG M.Bpddeke,et al.Induction of interleukin-1β mRNA after focal cerebral ischemia in the rat[J]Mol Brain Res,1994,23:126-134
[48]杜柏岩,关秀茹,高光强等.IL-1β对大鼠脑缺血再灌注损伤的意义[J]哈尔滨医科大学学报,2000(4)34,2:124-125
[49]周红,乔健.大鼠局灶性脑缺血再灌注纹状体内肿瘤坏死因子-α及白细胞介素-1β的动态变化[J]现代医学,2005,33(5),5:294-296
[50]Yamasaki Y,Metsuura N,Shozuhara H.et al.Interleukin-1 as a pathogenetic mediator of ischemic brain damage in rats.[J]Stroke,1995,26(4):676-680
[51]Wang X,Barone FC,Aiyar NV.et al.Interleuldn-1 receptor and receptor antagonist gene expression after focal stroke in rats[J]Stroke,1997,28(1):155-161
[52]Relton JK,Martin D,Thompson Re,et al.Peripheral administration of interleukin 1 receptor antagonist inhibits brain damage after focal cerebral ischemia in the rat.[J]Exp Neural,1996,138(2):206-13
[53]Hara H,Friedlander RM,Gagliaardini V,et al.Inhibition of interleukin 1 beta convening enzyme family proteases reduces ischemic and excitotoxie neuronol damage.[J]Proc Natl Acad Sci USA,1997,94(5):2007-2012
[54]Loddick SA,Mackenzie A,Rothwell NJ,et al.An ICE inhibitor Z-VAD-DCB attenuates ischemie brain damage in the rat[J]Neuroreport,1996,7(9):1465-1468
[55]STROEMER R P,ROTHWELL NT.Ortical protection by localized striatal injection of IL-1following cerebral ischemia in the rat[J].J Cereb Blood Flow Metab,1997,17:597-604
[56]王涛,陈莉,文亮.YVAD-FMK对大鼠全脑缺血再灌注后神经元损伤的影响[J]中国急救医学,2001,21(2),2:63-65
[57]李旦,孙桂莲,史金阳等.白细胞介素1β多克隆抗体对新生大鼠缺氧缺血性脑损伤的作用[J]卒中与神经疾病,1996,6,1:7-8
[58]王知秋,陈城,杨国源等.MEK抑制剂小鼠脑缺血后ERK通路的激活和IL-1β mRNA合成[J]复旦学报(医学版):2004,31(2):119-123
[1]Murry CE,Jennings RB,Reimer KA.Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium.Circulation,1986,74(5):1124-1136.
[2]Kitagawak K,Matssumoto M,Tagaya M.et al."Ischemia tolerance" phenomenon found in the Brain[J].Brain Res,1990;58:21-24.
[3]Monkayo J,de Freitas GR,Bogousslavsky J.et al.Do transient ischemic attacks have a neuroprotective effect? Neurology,2000,54(11):2089-2094.
[4]Kitagawa K,Matsumoto M,Kuwabara K.et al."Ischemia tolerance" phenomenon detected in various brain regions.Brain Res,1991,561:203-211.
[5]Glazier SS,O'Rourke DM,Graham DI.et al.Induction of ischemic tolerance following brief focal ischemia in rat brain.J Cereb Blood Flow Metab.1994,14:545-553.
[6]Miyashida K,Abe H,Nakajima T.Induction of ischemia tolerance in gerbil hippocampus by pretreatment with focal ischemia.Neuroreport.1994,6:46-48.
[7]Simon RP,Niiro M,Gwinn R.Prior ischemia stress protect against experimental stroke.Neurosci.Lett,1993,163:135-137.
[8]Barone FC,White RF,Spera PA.et al.Ischemia preconditioning and brain tolerance.Temporal histological and function outcomes,protein synthesis requirement,and interlukin-1 receptor antagonist and early gene expression.Stroke.1998,29:1937-1951.
[9]Masada T,Hua Y,Xi G.et al.Attenuation of ischemia brain edema and cerebrovascular injury after ischemia preconditioning in the rat.J Cereb Blood Flow Metab,2001,21(1):22-33
[10]Zhao HG,Li WB,LIQJ.et al.Limb ischemic preconditioning attenuates apotosis of pyramidal neurons in the CA1 hippocampus induced by cerebral ischemia-reperfusion in rats.Acta Physiologica Sinica,2004,56(3):407-412.
[11]Dawson DA,Furuya K,Gotoh J.et al.Cerebrovascular hemodynamics and ischemic tolerance:lipopolysaccharide-induced resistance to focal cerebral ischemia is not due to change in severity of the initial ischemia insult,but is associated with preservation of microvascular perfusion.J Cereb Blood Flow Metab,1999,19:1229-1237.
[12]Nawashiro H,Tasakik,Ruetzler CA.et al.TNF-alpha pretreatment induces protective effects against focal cerebral ischemia in mice.J Cereb Blood Flow Metab,1997,17(5):483-490.
[13]Masada T,Xi G,Hua Y.et al.The effects of thrombin preconditioning on focal cerebral ischemia in rats.Brain Res,2000,867(1-2):173-179.
[14]Toyoda T,Kassell NF,Lee KS.Induction of tolerance against ischemia reperfusion injury in the rat brain by preconditioning with the endotoxin analog diphosphoryl lipid A.J Neurosurg,2000,92:435-441.
[15]向强,文亮,高强国.内毒素预处理对大实权脑缺血/再灌注后炎性反应影响的实验研究.第三军医大学学报,2006,28(7):694-696.
[16]Lauritzen I,De Weille JR,Lazdunski M.The potassium channel openercromakalim prevents glutamate-induced cell death in hippocampal neurons.J Neurochem,1997,69:1570-1579.
[17]Shimizu K,Lacza Z,Rajapakse N.et al.MitoK(ATP) opener,diazoxide reduces neuronal damage after middle cerebral artery occlusion in the rat.Am J Physiol Heart Circ Physiol,2002,283:H1005-1011.
[18]Blondeau N,Plamondon H,Richelme C.et al.K(ATP) channel openers,adenosine agonists and epileptic preconditioning are stress signals inducing hippocampal neuroprotection.Neuroscience,2000,100:465-474.
[19]胡明,刘昌勤,冯作化.尼莫地平预处理和梗塞后治疗对大鼠脑缺血损伤保护作用的比较研究.脑与神经疾病杂志,2005,13(3)182-185.
[20]邬伟东,柴滢,王屹等.尼卡地平预处理大鼠脑缺血后神经细胞凋亡及其调控基因bcl-2的表达.中华创伤杂志,2005,(6),21,6:459-460.
[21]Lysko PG,Webb CL,Yue JL.et al.Neuroprotective effects of tetrodotoxin as a Na~+ channel modulator and glutamate release inhibitor in cultured rat cerebrallar neurons and in gerbil global brain ischemis.Stroke,1994,25(12):2476-2478.
[22]Grilli M,Pizzi M,Memo M.et al.Neuroprotection by aspirin and sodium salicylate through blockade of NF-κB activation.Science,1996,274(5291):1383-1385.
[23]Khayyam N,Thavendiranathan P,Carmichael FJ.et al.Neuroproetective effects of acetylsalicylic acid in animal model of focal brain ischemia.Neuroreport,1999,10(2):371-374.
[24]孙风云,闵连秋.阿司匹林预处理对局灶性脑缺血大鼠超氧化物歧化酶及丙二醛的影响.中国临床康复,2006,(10),30:162-163.
[25]罗祖明,郝玉曼.奥扎格雷钠对大鼠脑缺血耐受作用及核因子-κB表达的影响.中华老年医学杂志,2005,(2),24,2:134-136.
[26]Wise-Faberowski L,Raizada MK,Summners C.Oxygen and glucose deprivation-induced neuronal apoptosis is attenuated by haothane and isoflurane.Anesth Analg,2001,93:1281-1287.
[27]Kurth CD,Priestley M,Watzman HM.et al.Desflurane confers neurologic protection for deep hypothemic circulatory arrest in newborn pigs.Anesthesiology,2001,95:959-964.
[28]Kapinya KJ,Prass K,Dimagl U.Is flurane induced prolonged protection against cerebral ischemia in mice:a redox sensitive mechanism?Neuroreport,2002,13:1431-1435.
[29]吴明春,熊利泽,朱正华等.异氟醚预处理对脑保护作用的剂量-效应关系.第四军医大学学报,2002,23:1357-1359.
[30]Bhardwaj A,Alejandro F,Alkayed NJ.et al.Anesthetic choice of halo thane versus propofol:impact on experimental perioperative stroke.Stroke,2001,32(8):1920-1925.
[31]Kato H,Kogure K,Araki T.et al.Astroglial and nucroglial reactions in the gerbil hippocampus with induced ischemic tolerance.Brain Res,1994,664(1-2):69-76.
[32]Kobayashi S,Harris VA,Welsh FA.Spreading depression induces tolerance of cortical neurons to ischemia in rat brain.J Cereb Blood Flow Metab.1995,15:721-727.
[33]Otori T,Greenberg JH,Welsh FA.Cortical spreading depression causes a long-lasting decrease in cerebral blood flow and induces tolerance to permanent focal ischemia in rat brain.J Cereb Blood Flow Metab.2003,23:43-45.
[34]Yanamoto H,Hashimoto N,Nagata I.et al.Infarct infarct tolerance against temporary focal ischemia following spreading depression in rat brain.Brain Res,1998,784(1-2):239-49.
[35]胡学斌,赵洪洋,冯哲等.皮层扩散性抑制预处理对大鼠脑缺血性损伤的保护作用.中华实验外科杂志,2006,(8),23,8:968-970.
[36]Nishio S,Yunoki M,Chen ZF.et al.Is-chemic tolerance in the rat neocortex following hypothermic preconditioning.J Neurosurg,2000,93(5):845-851.
[37]Xu H,Aibiki M,Nagoya J.Neuroprotective effect of hyperthermic preconditioning on infracted volume after middle cerebral artery occlusion in rats:role of adenosine receptors.Crit Care Med,2002,30(5):1126-1130.
[38]Uno H,Kobayashi H,Handa Y.et al.Alterations of calciumcal modulin dependent protein kinase Ⅱ activity in ischemia induced neuronal death and neuronal protection against ischemia in the gerbil hippocampus.Acta Neurochir,1999,141:287-294.
[39]Mu D,Chang YS,Vexler ZS.et al.Hypoxia-inducible factor 1 alpha and erythropoietin upregulation with deferoxamine salvage after neonatal stroke.Exp Neurol,2005,195(2):407-415.
[40]Prass K,W jegand F,Schumann P.et al.Hyperbaric oxygenation induced tolerance against focal cerebral ischemia in mice is strain dependent.Brain Res,2000,87(1):146-150.
[41]Aketa S,Nakase H,Kamada Y.et al.Chemical preconditioning with 3-nitropropionic acid in gebil hippocampal Slicea the-apeutic window and the participation of adenosine receptor.Exp Neurol,2000,166(2):385-391.
[42]Xiong L,Zhu Z,Dong H.et al.Hyperbaric oxygen preconditioning induces neuroprotection against ischemia in transient not permanent middle cerebral artery rat model.Chin Med J
[43]Wardsa J.Neuroprotective role of adenosine in the CNS.Pol J Pharmacol,2002,54:313-326.
[44]Simon RP,Cho H,Gwinn R.et al.The temporal profile of 72-kDa heat-shock protein exprcssion foUowing global ischemia.J Neurosci,1991,11(4):881-889.
[45]Currie RW,Ellison JA,White RF.et al.Benign focal ischemic preconditioning induce neuronal hes70 and prolonged astrogliosis with expression of hsp72.Brain Res,2000,863(1-2):169-181.
[46]Kitagawa K,Matsumoto M,Kuwabara K.et al.Ischemic tolerance phenomenon detected in various brain regions.Brain Res,1991,561(2):203-211.
[47]Chen J,Graham SH,Zhu RL.Stress protein and tolerance to focal cerebral ischemia.J Cereb Blood Flow Metab,1996,16(4):566-567.
[48]Vass K,Welch NJ,Nowak TS Jr.et al.Localization of 70-Kda stress protein induction in gerbil after ischemia.Acta Neuropathol Berl,1998:77:128.
[49]Kirino T.et al.J Cereb Blood Flow Metab,1991;11(2):299.
[50]Kane DJ,Ord T,Anton R.et al.Expression of bcl-2 inhibits necrotic neural cell death.J neurosci Res,1995,40(2):269-275.
[51]Kobayashi S,Harris VA,Welsh FA.Spreading depression indueces tolerance of conical neurons to ischcmia in rat brain.J Cereb Blood Flow Metab,1995,15(4):721-727.
[52]Pringle AK,Thomas SJ,Signorelli F.et al.Ischemic pre-conditioning in organotygic hippocampal slice cultures in inversely correlated to the induction of the 72-Kda heat shock protein(HSP72). Brain Res,1999,845(2):152-164.
[53]Douen AG,Akiyama K,Hogan MJ.et al. preconditioning with cortical spreading depressing decrease intraischemic cerebral glutamate levels and down-regulates excitatory amino acid transporters EAAT1 and EAAT2 from rat cerebral cortex plasma membranes. J Neurochem, 2000,75:812-818.
[54]Crabb MC, Choi DW. Ischeraic tolerance in murine cortical cell culture: critical role for NMDA receptors. J Neurosci, 1999,19:1657-1662.
[55]Alsbo CW, Wrang ML, Nielsen M. et al. Ischemic tolerance affects the adenylation state of GluR2 Mrna. Neuroreport,2000,11:3279-3282.
[56]Vanux DL,Strasser A. The molecular biology If apoptosis. Proc Natl Acad Sci USA.1996,193:2239-2244.
[57]Shimizu S,Eguchi Y.Kosaka H. et al. Prevention of hypoxia induced cell death by bcl-2 and bcl-x. Nature. 1995,374:811-813.
[58]Chen J,Graham SH,Nakayama M. et al. Apoptosis repressor genes bcl-2 and bcl-x are expressed in the rat brain following global ischemia. J Cereb Blood Row Metab.1997,17:2-10.
[59]Shimazki K,Ishida A,Kawai N. Increase in bcl-2 oncoprotein and the tolerance to ischemia-induced neuronal death in the geril hippocampus. Neurosci Res.l994,20(l):95-99.
[60]Oltvai ZN,Milliman CL,Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell, 1993;74(4):609-19.
[61]Oltvai ZN,Millman CL,Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, bax that accelerates programmed cell death. Cell. 1993,74:609-619.
[62]Tomasevic G,Sham loo,Istaeli D.et al.Activation of p53 and its target p21 (W AF1/C ipl) and PAG608/W jg-1 in ischemic preconditioning Brain Res Mol Brain Res,1999,70(2):304-313.Expression of BCL-2 inhibibits necrotic neural cell.death.
[63]Zhang RZ,Wu, C,Fujihara H. et al. Both acspase-dependent and caspase-independent pathways may be involved in hippocampal CA1 neuronal death because of loss of cytochrome c From mitochondria in a rat forebrain ischemia model. J Cereb Blood Flow Metab,2001;21(5):529-40.
[64]Liu J,Ginis I,Spatz M. et al. Hypoxic preconditioning protects cultured neurons against hypoxic stress via TNF-alpha and ceramide. Am J Physiol Cell Physiol.2000,278(l):C144-53.
[65]Shamloo M, Rytter A, Wieloch T. Activation pf the extracellular signal-regulated protein kinase cascade in the hippocmpal CA1 region in a rat model of global cerebral ischemic preconditioning. Neuroscience. 1999, 93(1) :81-8
[66]Gonzale-Zuleeta M,Peldman AB,Klesse LJ. et al. Requirement for nitric oxide activation of 21ras/extracellular regulated kinase in near ronal ischemic preconditioning. Proc. Natl Acad Sci USA,2000,97(1):436-441.
[67]Toyoda T,Kassell NF,lee KS. et al. Induction of ischemic tolerance and antioxidant activity by brief focal ischemia. Neuro Report,1997,8(4):847-851.
[68]Lascola C,Kraig RP.et al. Astroglial acid-basedynamics in hyperglycemic and normoglyceic global ischemia. Neurosci Biobehav Rev,1997,21:143-50.
[69]Schurr A,Payne RS,Miller JJ.et al. Glia are the main source of lactate utilized bu neurons for recovery of function posthypoxia.. Brain Res,1997,74,221-4.
[70]Kato H,Kogure K,Araki T. et al. AS troliat and microglial reactions in the gerbil hippocampus with induced ischemic tolerance.Brain Res,1994,664:69-76.
[71]Liu J,Bartels M,Lu A.et al.Microglia/macrophages prolife rate in striatum and neocortex but not in hippocampus after brief global ischemia that produces ischemie tolerance in gerbil brain.J Cereb Blood Flow Metab,2001,21(4):361-73.
[72]Nakata N,Kato H,Kogure K.Effects of repeated cerebral ischemia on extracellular amino acid concentrations measured with intracerebral microdialysis in the gerbil hippocampus.Stroke,1993(3),24:458-464.
[73]Barone FC,White RF,Spera PA.et al.Ischernie preconditioning and brain tolerance:temporal histological and functional outcome,protein synthesis requirement,and inteleukin-1 receptor anatagonist and early gene expression.Stroke,1998,29(9):1937-1951.
[74]Belayev I,Ginsberg MD,Alonso OF.et al.Bilateral isehemie tolerance of rat hippocampus induced by prior unilateral focal ischemia:relationship to c-fos Mrna expression.Neuroreport:1996,8(1):55-59.
[75]Gonzale-Zuleeta M,Peldman AB,Klesse LJ.et al.Requirement for nitric oxide activation of 21ras/extracellular regulated kinase in near renal ischemie preconditioning.Proc.Natl Acad Sci USA,2000,97(1):436-441.
[76]Whitefield PC,Williams R,Pickard JD.et al.Delayed induction of JunB precedes CA_1neuronal death after global ischernia in the gerbil.Brain Res.1999;818(2):450-458.
[77]Okimura Y,Tanno H,Fukduda K.et al.Reactive astrocytes in acute stage after experimental brain injury:relationship to extravasated plasma protein and expression of heat shock protein.J Neurotrauma,1996;13(7):385-393.
[78]Chen D,minami M,Henshall DC.et al...U pregulation of mitoehoir drial base-ezeision repair capability within rat brain brief ischemia.J Cereb Blood Flow Metab,2003,23:88-98.
[79]Iwai M,Hayashi T,Zhang WR.et al.Induction of highly polysialylated neural cell adhesion molecule(PSA-NCAM) in postischemie gerbil hippocampus mainly dissociated with neural stern cell proliferation.Brain Res,2001,902(2):288-293.
[80]Jin K,Minami M,Lan JQ.et al.Neurogenesis in dentate subgranular zone and rostral subventriculture zone after focal cerebral isehemia in the rat.Proc.Natl Acad Sci USA.2001,98:4710-4715.
[81]鄢文海,陈正跃,崔景彬等.β淀粉样蛋白诱导胚胎大鼠神经干细胞凋亡.实用儿科临床杂志,2004,19(8):658-659.
[82]Teacher AB,Yamashima T,Zhao L.et al.Proliferation of neural and neuronal progenitors after global brain isehemia in yong adult macaque monkeys.Mal Cell Neurosci,2003,23(2):292-301.
[83]Arvidsson A,Kokaia Z,Lindvall O.N-methyl-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke.Eur J Neurosci,2001,14(1):10-18.
[84]Orendacova J,Racekova E,Kucharova K.et al.Ependyma as a possible morphological basis of ischemic preconditioning tolerance in rat spinal cord ischemia model:nestin and Fluoro-Jade B observation.Cell Mal Neurobiol,2004,24(3):477-489.
[85]Chimon GN,Wong PT.Ischemie tolerance and lipid peroxidation in the brain.Neuroreport,1998,9(10):2268-2272.
[86]Toyoda T,Kassell NF,Lee KS.Induction of ischemic tolerance and antioxidant activity by brief of focal ischemia.Neuroreport,1997,8(4):847-851.
[87]Mori T,Muramatsu H,Matsui T.et al.Possible role of the superoxide anion in the development of neuronal tolerance following ischemie preconditioning in rats.Neuropathol Appl Neurobiol,2000,26(1):31-40.
[88]Honthius DJ,steward O.Induction of cortical spreading depression with potassium chloride upregulatcs levels of messenger RNA for glial fibrillary acidic protein in cortex and hippocampaus:inhibition by MK-801.Brain Res.1993:618:83-94.
[89]Katayama Y,Muramatsu H,Kamuya T.et al.Ischemic tolerance phenomenon from an approach of energy metabolism and the mitochondrial enzyme activity of pyruvate dehydrogenase in gerbil.Brain Res,1997,746:126-132.