芦荟多糖对大鼠局灶性脑缺血损伤的保护作用研究
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摘要
目的：观察芦荟多糖对局灶性脑缺血大鼠的神经保护作用，并进一步探讨其作用机制。
方法：采用线栓法阻断大鼠一侧大脑中动脉(MCAO)，制备局灶性脑缺血模型，观察芦荟多糖对MCAO模型大鼠脑缺血后24h神经功能缺损导致的行为学变化，通过HE染色及透射电镜观察MCAO模型大鼠脑组织病理形态学变化，此外还通过流式细胞仪检测芦荟多糖对MCAO模型大鼠脑缺血后24h大脑皮质细胞凋亡率的影响，并以免疫组化法检测芦荟多糖对其大脑皮质Caspase-3、COX-2、NF-κBp65、ICAM-1蛋白表达的影响，以此探讨芦荟多糖对脑缺血的神经保护作用及其作用机制。
结果：芦荟多糖能明显改善MCAO模型大鼠神经功能缺损的症状和脑缺血组织的病理形态学变化，降低缺血脑组织的凋亡率，抑制NF-κBp65、ICAM-1、Cox-2、Caspase-3蛋白表达。
结论：芦荟多糖对大鼠局灶性脑缺血具有保护作用，其机理可能与芦荟多糖抗炎和抑制神经元细胞凋亡有关。
Objective:To study and explore the neuroprotective effects and thefurther mechanism of polysaccharide of Aloe barbadensis(PAB) oncerebral ischemia in rats.
Methods:In order to observe the neuroprotective effect of PAB oncerebral ischemia,the rats with incomplete cerebral ischemia were inducedwith fishing lines in the middle cerebral artery(MCA) and then wereexecuted at 24h after cerebral ischemia.It was observed the effect of PABon the changes of ethology and pathomorphology due to nerve injury ofrats with MCAO before and after treatments.HE staining was used toobserve the changes of histomorphology.Electronic microscopy was usedto study the ultrastructure of areas.It was detected the effects of PAB onprotein expression ofcysteinyaspartate specificprotease-3(Caspase-3),Cyclooxygenase-2(COX-2),Nuclear Factor Kappa B p65(NF-κB p65)and intercellular adhesion molecule-1(ICAM-1) with immunohistochemicalmethod.In addition,we observe the rate of cell apoptosis with flowcytometry.
Results:PAB could make obviously pathomorphology of cerebralischemia better,improve change of ethology,decrease the rate of cellapoptosis of ischemic cerebral tissue,inhibit the expression of cysteinyaspartate specific protease-3(Caspase-3),Cyclooxygenase-2(COX-2),Nuclear Factor Kappa B p65(NF-κB p65) and intercellular adhesionmolecule-1(ICAM-1) protein in cerebral cortex to protect the nerves aftercerebral ischemic injury of rats.
Conclusion:PAB had protecting effect on cerebral ischemia,themechanism of PAB against cerebral ischemia is related toanti-inflammatory action and inhibiting cell apoptosis.
方法：采用线栓法阻断大鼠一侧大脑中动脉(MCAO)，制备局灶性脑缺血模型，观察芦荟多糖对MCAO模型大鼠脑缺血后24h神经功能缺损导致的行为学变化，通过HE染色及透射电镜观察MCAO模型大鼠脑组织病理形态学变化，此外还通过流式细胞仪检测芦荟多糖对MCAO模型大鼠脑缺血后24h大脑皮质细胞凋亡率的影响，并以免疫组化法检测芦荟多糖对其大脑皮质Caspase-3、COX-2、NF-κBp65、ICAM-1蛋白表达的影响，以此探讨芦荟多糖对脑缺血的神经保护作用及其作用机制。
结果：芦荟多糖能明显改善MCAO模型大鼠神经功能缺损的症状和脑缺血组织的病理形态学变化，降低缺血脑组织的凋亡率，抑制NF-κBp65、ICAM-1、Cox-2、Caspase-3蛋白表达。
结论：芦荟多糖对大鼠局灶性脑缺血具有保护作用，其机理可能与芦荟多糖抗炎和抑制神经元细胞凋亡有关。
Objective:To study and explore the neuroprotective effects and thefurther mechanism of polysaccharide of Aloe barbadensis(PAB) oncerebral ischemia in rats.
Methods:In order to observe the neuroprotective effect of PAB oncerebral ischemia,the rats with incomplete cerebral ischemia were inducedwith fishing lines in the middle cerebral artery(MCA) and then wereexecuted at 24h after cerebral ischemia.It was observed the effect of PABon the changes of ethology and pathomorphology due to nerve injury ofrats with MCAO before and after treatments.HE staining was used toobserve the changes of histomorphology.Electronic microscopy was usedto study the ultrastructure of areas.It was detected the effects of PAB onprotein expression ofcysteinyaspartate specificprotease-3(Caspase-3),Cyclooxygenase-2(COX-2),Nuclear Factor Kappa B p65(NF-κB p65)and intercellular adhesion molecule-1(ICAM-1) with immunohistochemicalmethod.In addition,we observe the rate of cell apoptosis with flowcytometry.
Results:PAB could make obviously pathomorphology of cerebralischemia better,improve change of ethology,decrease the rate of cellapoptosis of ischemic cerebral tissue,inhibit the expression of cysteinyaspartate specific protease-3(Caspase-3),Cyclooxygenase-2(COX-2),Nuclear Factor Kappa B p65(NF-κB p65) and intercellular adhesionmolecule-1(ICAM-1) protein in cerebral cortex to protect the nerves aftercerebral ischemic injury of rats.
Conclusion:PAB had protecting effect on cerebral ischemia,themechanism of PAB against cerebral ischemia is related toanti-inflammatory action and inhibiting cell apoptosis.
引文
[1]张国瑾，赵增荣．国外脑血管疾病研究进展[M]．北京：中国医药科技出版社，2000，177—197．
[2]周鸿雁，毛海峰，王一蓉，等．脑缺血损伤的研究进展[J]。湖南文理学院学报，2005，17(2)，72-75．
[3]张晓琴、章军建．神经病学．武汉大学出版社，2002，6：117-118．
[4]Chan PH.Reactive oxygen radicals in sigaling and damage in the ischemic brain[J].J Cereb Blood Flow Metab,2001,21(1):2-14.
[5]Lewen,Matz P,Chan PH.Free radical pathways in CNS injury [J].J Neurotrauma,2000,17(10):871-890.
[6]陈敏，李长清，胡长林，等．钙与脑缺血／再灌注后神经细胞凋亡[J]．脑与神经疾病杂志，2003，11(4)：253-255．
[7]Lewen A,Matz P,Chan PH.Free radical pathways in CNS injury [J].Neurotrauma,2000,17 (10) :871-890.
[8]Hignchi Y.increase in NO in the hypoxic-ischemic neonatalrat brain and supperession by 7-N1 and aminoguanidine[J].Eue J Pharmacol,1998,342(1):47-49.
[9]Kumura M,Inao S,Takayasu M,et al.Time course of expression of the three nitric oxide synthase isoforms after transient middle cerebral arteryocclusion in rats[J].Neurol Med Chir(Tokyo),2001,41(2):63-72.
[10]De Alba J,Cardenas A,Moro MA,et al.Down-regulation of neuronal nitric oxide synthase by nitric oxide after oxygen-glucose deprivation in rat forebrain slices[J].J Neurochem,1999,72(1):248-254.
[11]苏志达，李瑜，李宏建．卒中治疗药物临床前的实验研究[J]．国外医学脑血管疾病分册，2000，8(5)：290-293．
[12]高维娟．大鼠脑缺血再灌注后海马组织兴奋性氨基酸含量的动态观察．承德医学院学报，2003，20(3)：155—187．
[13]蔡竖平，桂秋萍，韩志涛，等．脑缺血-再灌注后海马迟发性神经元死亡的实验研究[J]．军医进修学院学报，2002，23(4)：268-270．
[14]张焰，陈群，顾卫东，等．灯盏花素对脑缺血再灌注沙土鼠兴奋性氨基酸释放 和学习记忆能力的影响[J]．中华实用中西医杂志，2004，4(17)：1930-1932．
[15]陈敏，李长清，胡长林，等．钙与脑缺血／再灌注后神经细胞凋亡[J]．脑与神经疾病杂志，2003，11(4)：253-25 5．
[16]Kinouchi H,Huang H,Arai S,et al.Induction of cyclooxygenase-2 messenger RNA after transient and permanent middle cerebral artery occlusion in rats:comparison with c-fos messenger RNA by using in situ hybridization [J].Neurosurg,1999,91 (6):1005-1012.
[17]VilanN,Castillo J,Davalos A,et al.Proinflammatory cytokines and early neurological Worsening in isehemic stroke.Stroke.2000,31(10):2325-2329.
[18]Stephenson D,Yin T,Smalstig EB,et al.Transcription factor Nuclear Factor Kappa B is activated in neurons after focal cerebral ischemia [J].Cere Blood flow Metab,2000,20 (3) :592- 603.
[19]冯春生，麻海春，岳云，等．异丙酚对大鼠局灶性脑缺血再灌注时核因子κB的活化和炎症因子表达的影响[J]．中华医学杂志，2004，84(24)：2110
[20]Clemens JA,Stephenson DT,Dixon EP,et al.Global cerebral ischemia activates nuclear factor-kappa B prior to evidence of DNA fragmentation [J].Mol Brain Res,1997,48 (2) :187-196.
[21]田代实， 王光海，郭国际．核因子κB在大鼠脑缺血耐受中的作用及其对细胞间黏附分子-1和Bcl-2表达的影响[J]．中风与神经疾病杂志，2004，21(3)：205-207．
[22]Nicolas B,Catherine W,Michel L,et al.Activation of the nuclear factor κB is a key event in brain tolerance [J].Neurosci.2001,21 (13) :4668-4677.
[23]Perkins ND.The Rel/ NF-kappa B family:friend and foe [J].Trends Biochem Sci,2000,25 (9) :434-440.
[24]Nogawa S,Zhang F,Ross ME,et al.Cyclooxygenase-2 gene expression in neurons contributes to ischemic brain damage [J].Neurosci,1997,17 (8) :2746-2755.
[25]Iadecola C,Forster C,Nogawa S,et al.Cyclooxygenase-2 immunoreactivity in the human brain following cerebral ischemia [J].Acta Neuropathol (Berl),1999,98 (1) :9-14.
[26]Kaufmann WE,W orley PF,Pegg J,et al.COX-2,a synaptically induced enzyme,is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex [J].Proc Natl Acad Sci USA,1996,93 (6) :2317-2321.
[27]李琴，张云，郭云良，等．肌苷对脑缺血再灌注后COX-2表达的调节作用[J]．中国老年医学杂志，2004，17(8)：640-711．
[28]Sasaki T,Kitagawa K,Yamagata K,et al.Amelioration of hippocampa neuronal damage after transient forebrain ischemia in cyclooxygenase-2 deficient mice [J].Cerebral Blood Flow Metab,2004,24 (1) :107-113.
[29]Kinoshita Y,Ueyama T,Senba E,et al.Expression of c-fos,heat shock protein 70,neurotrophins and cyclooxygenase-2 mRNA in response to focal cerebral ischemia/reperfusion in rats and their modification by magnesium sulfate [J].Neurotrauma,2001,18 (4) :435-445.
[30]Miettinen S,Fusco FR,Yrjanheikki J,et al.Spreading depression and focal brain ischemia induce cyclooxgenase-2 in cortical neurons through N-methyl-D-aspartic acid-receptors and phospholipase A2 [J].Proc Natl Acad Sci USA,1997,94 (12) :6500-6505.
[31]Mirjany M,Ho L,Pasinetti GM.Role of cyclooxygenase-2 in neuronal cellcycle activity and glutamate-mediated excitotoxicity [J].Pharmacol Exp Ther,2002,301 (2) :494-500.
[32]Nishikawa M,Stapleton PP,Freeman TA,et al.NS2398 inhibits tumor growth and liver metastasis of colon cancer through induction of apoptosis and suppression of the plasminogen activation system in a mouse model [J].Am Coll Surg,2004,199 (3) :428-435.
[33]Hunot S,Vila M,Teismann P,et al.JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease [J].PNAS,2004,101 (2):665-670.
[34]Sobel RA,Mitchell ME,Fonder G,Intercellular adhesion molecule (ICAM-1) in cellular immune reactions in the human central nervous system[J].Am-J-Pathol,1990,136 (6) :1309-1316.
[35]Chen CC,Rosenbloom CL,Imuro Y,et al.Ihibition of NF kappaB in activated rat hepatic stallate cells by proteasome inhibitors and an IkappaB super-repressor [J].Hepatology,1998,27 (5) :1285-95.
[36]Park,CW,Nico B,Trojano M,et al.High glucose-induced intercellular adhesion molecule (ICAM-1) expression through an osmotic effect in rat mesangial cells is PKC-NF-kappa B-dependent [J].Diabetologia,2000,43( 12):1544-1553.
[37]郝延磊，，蒲传强，张凤英，等．实验性脑缺血模型脑组织微血管细胞间粘附分子1表达的研究[J]．中华神经科杂志，1998，31(2)：105．
[38]郝延磊，蒲传强，朱克，等．细胞间粘附分子1和E选择素在局部脑缺血中的作用[J]．中华老年心脑血管病杂志，2000，2(1)：54-5 7．
[39]吴珊，董为伟，董佑忠．局灶脑缺血再灌流后ICAM-1表达于白细胞浸润[J]．中风与神经病杂志，2000，17(1)：5-7．
[40]叶诸榕．脑缺血的细胞死亡：坏死或凋亡．中华神经科杂志[J]，1998，31(5)：301-304．
[41]Wyllie A.H.,“Apoptosis(the 1992 Frank Rose Memorial Lecture)” ,Br J Cancer,1993,67 (2) :250-208.
[42]Arends M．J．，Wyllie A．H．，”Apoptosis：mechanisms and roles in pathology”，Int Rev Exp Pathol，1991，32：223-254．
[43]刘煜敏，徐仁，黄怀钧，等．兴奋性氨基酸、氧自由基与缺血再灌注损伤关系的实验观察[J]．卒中与神经疾病，2001，7(2)：98-100．
[44]Watson M,Yanlalllura HI,Roeske WR.A unique regulatory profile and regional distribution of pirenzepine binding in the rat provide evidence for distinct difference for apoptosis and necrosis[J].Life Sci,1983,32(4):3001-3011.
[45]Garcia JH,Ye ZR,Liu KE.Delayed neuronal death in experimental Ischemicstroke [M].In:ToUetal.eds:Maturation phenomenon in cerebral ischemia.Berlin:Springer-Verlag,2002,25(6):267-273.
[46]Harrison W,Beyaert R,Declercq W,Vandenabeele P.More than one way to die:apoptosis and necrosis and reactive oxygen damage[J].Onco gene,1999,18(54):7719-7730.
[47]Li Y,Chopp M,Powers C,et al.Apoptosis and protein expression after Foc 1 cerebral ischemia reperfussion in rats [J].Brain Res, 1997,765(2) :301.
[48]Hayashi Y,Tikhara I,Yagi T,et al. Immunohistochemical investigation of caspase-1 and effect of caspase-1 inhibitor in delayed neuronal death after transient cerebral ischemia[J]. BrainRes, 2001,893(2) : 113-120.
[49]Corman AM.Orreeniu S,Ceccatelli S.Apoptosis in neuronal cells:role of Caspase [J].Neuroreport, 1998,9:49-55.
[50]White BC,Sullivan JM, Degracia DJ, et al.Brain ischmia and reperfussion:molecular mechanisms of neuronal injury[J].J Neurol Sci, 2000,179(2) : 1-33.
[5l]Hartmann A,Hunot S,Michel PP.caspase-3:A vunerability factor and final effector in apoptotic death of dopeminergic neurons in Paekinson' sdisease[J].Proc Natl Acad SciUSA,2000,97 (6) :2875-2880.
[52]Harrison DC, Davis RP,Bond BC,et al. Caspase mRNA expression in ratmodel of focal cerebral ischemia reperfussion[J].Brain Res Mol, 2001,89(1):133-146.
[53] Sugawara T, Fujimura M, Morita-Fujimura Y, et al. Mitochondrial release of cytochrome c corresponds to the selective vulnerability of hippocampal CA1 neurons in rats after transient global cerebral ischemia [J]. Neurosci, 1999, 19(22): RC39.
[541 Antonawich FJ. Translocation of cytochrome c following transient global ischemia in the gerbil [J|. Neurosci Lett, 1999, 274 (2):123-126.
[55] Maeda K, Hata R, Gillardon F, et al.Aggeavation of brain injury after transiene focal ischemia in p53-deficient mice [J]. Brain Res Mol Brain Res, 2001, 88(1-2) : 54-61.
[56] GuptaS, Knowlton AA. HSP60, Bax, apoptosis and the heart [J]. Cell Mol Med,2005, 9(1): 51-58.
[57] Graham SH, Chen J, Clark RS. Bcl-2 family gene productd incerebral ischemia and traumatic brain injury [J]. Neurotrauma, 2000, 17 (10) : 831-841.
[58] Shimizu S, Nagayama T, Jin K.L, et al. Bcl-2 antisense treatment prevents induced of tolerance to focal ischemia in the rat brain [J]. Cereb Brain Flow Metab, 2001, 21 (3) : 233-243.
[59] Liu D, Lu C, Wan R, et al. Activation of mitochondria) APT-dependent potassium channels products neurons against ischemia-induced by a mechanism involve suppression of Bax translocation and cytochrome C release [J]. Cereb Blood Flow Metab, 2002, 22 (4) : 431-443.
[60] Takemoto O. Tomimoto H, Yanagihara T. Induction of c-fos and c-jun gene products and heat shock protein after brief and prolonged cerebral ischemia in gerbils [J]. Stroke, 1995, 26 (9) : 1639-1648.
[61] Dragunow M, Beilharz E, Sirimanne E, et al. Immediate early gene protein expression in neurons undergoing delayed death, but not necrosis, following hypoxic ischemic injury to the young rat brain [J]. Brain Res Mol Brain Res,1994, 25 ( 1—2) : 19-33.
[62] Whitfield J, Neame SJ, Paquet L, et al. Dominant-negative c-Jun promotes neuronal survival by reducing B I M expression and inhibiting mitochondrial cytochrome c release [J]. Neuron, 2001, 29 (3) : 629-643.
[80] Li Y, Chopp M, Power C, et al. Apoptosis and protein expression after focal cerebral ischemia in rat[J]. Brain Res, 1997, 15: 301.
[81] Maeda K, Hata R, Gillardon F, et al. Aggravation of brain injury after transient focal ischemia in p53-deficient mice [J]. Mol Brain Res, 2001,88: 54-61.
[82] Looderen V, Campagne M, GilL R. Cell cycle-related gene expression in the adult rat brain selective induction of cyclin G1 and p21 WAFI/CIPI in neurons following focal cerebral ischemia [J]. Neuroscience, 1998, 84: 1097.
[83] Miyashiton T, Harigai M, Hanada Metal. Identification of a p53-dependent negative response element in the bcl-2 gene[J]. Cancer Res, 1994, 54: 3131.
[85] Min H J , Tomohori Kaku, Junichi Hada, el al. Different effects of eNOS and nNOS inhibition on transient forebrain ischemia [J]. Brain Res, 2002, 946 :139-142.
[86]Vaughan CJ ,Delanty N ,Basson CT.Statin therapy and stroke Prevention[J].CurrOpin Carrdiol,2001,(4):219—228.
[87]Oconnell AW ,Fox GB ,Kjoiler C ,el al.Antiischemic and cognition-enhancing properties of NNC-711.agamma-arninbutyricacid reccptakeinhibitor [J].Eur J Pharmacol,2001,424(1):37—43.
[88]Eguchik,Kariok.Shimada K Beneficial effect of ARB of ischemic stroke [J].Nippon Rinsho ,2002,60(10) :1987— 1998.
[89]Ferrer I,Planas AM.Signaling of cell death and cell survial following focal cerebral ischemia:life and death struggle in the penumbra[J].J Neuropathol Exp Neurol,2003,62(4):329-339.
[90]DuG,Zhang J.Protective effects of salvianolic acid A against impairment of Memory induced by cerebral isehemia-reperfusion in miee.Chin Med J(Engl).1997,110(1):65-68.
[91]Li l.Protective effects of schisanhenol,salvianolic aeid A and SY-L on oxidative Stress induced injuries of cerebral cells and their mechanisms.Sheng Li Ke Xue Jin Zhan.1998,29(1) :35-8.
[92]Yagi A,et al.Chem,Pharm Bull.1977,25(7):1770.
[93]万金志．芦荟的化学成分及其研究．中草药，1999，30(2)：151．
[94]Bill H,Meanalley.US,5:468,737.
[95]An Susun,etc.Sci.conf.Asian Soc.Cosmet.Sci3rd.1997:70-73.
[96]Heggers John P,etc.Phytother.Res,1995,9(6) :455-457.
[97]Kenshi Fukuyasu,etc.Fragrance[J].1995,23(8) :82-85.
[98]W.Olechnowiez-Stepien,etc.HerbaPol.1988,34(1) :35-42.
[99]Shihokokaku.etc.Biosei,Bioteehnol,Bioehem.1997,61 (3) :558-560.
[100]冈田和也．日癌疗治．1994，29(8)：1191．
[101]李伟芳．中国中药杂志．1991，16(11)：688．
[102]王官．福建中医．1991，22(1)：44-45．
[103]王宝成．人民军医．1996，4：40．
[104]Yushi Sato，etc．(日本)药学杂志．1990，110(11)：876-884．
[105]Hlroshi Hikino，etc．(日本)药学杂志 0553．1989，109(5)：335-339．
[106]邓小云，丁登峰，戴美红，等．植物多糖药理作用研究进展．中医药导报，2006， 12(9):86-88.
[107]Roberts DB,Travis EL.Acemannan-containing wound dressing gel reduces Radiation-induced skin reactions in C3H mice[J].Int J Radiat Oneol Biol Phys,1995,32(4):1047-1052.
[108]Kahion JB,Kem PMC,Carpenter PH,et al.Inhibition of AIDS virus replication by acemannan in vitro[J].Mol Biother.1991,3(3):127-135.
[109]Montaner JS,Gill J,Singer J,et al.Double-blind placebo-controlled pilot trial of acemannan in advanced human inununodeficiency virus disease[J].J Acquir Immune DefiC Syndr Hum Retrovirol.1996 ,12(2):153-157.
[110]Thomas DR,Goode PS,LaMaster K,et al.Acemannan hydrogel dressing versus saline Dressing for pressure uleers.A randomized,controlled trial[J].Adv Wound Care,1998,11(6):273-276.
[111]Saito H,Imanishi K,Okabe S.EffeCts of aloe extracts,aloctin A,on gastric secretion and on experimental gastric lesions in rats[J].Yakugaku Zasshi,1989,109(5):335-339.
[112]信照亮．鼠急性脑缺血的实验研究进展[J]．国外医学神经病学神经外科学分册，1991，18(2)：90-93．
[113]陈春富．大鼠局灶性脑缺血模型研究进展[J]．国外医学脑血管病分册，1995，3(5)：227-230．
[114]ponien U,Rateheson RA,Salford LG Optimal freezing conditions forcerebral Metabolites in rats[J].Neuxochem,1973,21(5):1127-1138.
[115]Eklof B,siesjo BK.The effct of bilateral earotid artery ligation on the blood flow and energy state of the rat brain[J].Aeta Physiol Seand,1972,86(2):155-165.
[116]Eklof B,Siesjo BK.Cerebral blood flow in isehemia eaused by carotid artery ligation in the rat[J].Aeta Physiol Seand,1973,87(1):69-77.
[117]Nordstrom GH ,SiesjoBK Effcts of Phenobarbital in cerebral isehemia[J].PartⅠ：Stroke,1978,9(4)：327-335.
[118]王蕊，杨秦飞，唐一鹏，等．大鼠拟血管性痴呆模型的建立及中药9602防治作用初探[J]．北京中医药大学学报，2000，23(5)：30-30．
[119]傅建华，杜贵友．天麻促智颗粒对反复脑缺血再灌小鼠脑组织递质性氨基酸含量的影响[J]．中国中药杂志，2001，26(1)：53-55．
[120]任德成，杜冠华，张均田．总丹酚酸对脑缺血再灌注损伤的保护作用[J]．中国药理学通报，2002，18(3)：275-277．
[121]Pulsineli WA,Brieley JB.A new model of bilateral hemispheric isehemia in the Unanesthetized rat[J].Stroke,1979,10(3):267-272.
[122]Maerae I M.New models of foeal cerebral ischemia[J].Br J Clin Pharmaeol,1992,34(4):302-308.
[123]Kameyama M,Suzuki J,Shirane R,et al.A new model of bilateral hemispheric isehemia in the rat-three vessel occlusion model[J].Stroke,1985,16(3):489-493.
[124]李威，范军铭，贾士奇，等．电针对大鼠全脑缺血再灌流损伤的保护作用[J]．中国针灸，1996，36(11)：211-213．
[125]王军，马开，屠万倩．电针对全脑缺血再灌流大鼠脑组织氨基酸递质的影响[J]．辽宁中医杂志，2007，34(2)：226-225．
[126]Tamura A,Graham D1,McCulloch J,et al.Foeal cerebral isehemia in the rat:1.DeseriPtion of teehnique and early neuroPathologieal consequences following middle Cerebral artery occalusion[J].J Cerb Blood Flow Metab,1981,1(1):53-60.
[127]TAmura.A,Graham DI,McCulloeh J,et al.Foeal cerebral isehaemia in the rat:2.Regional cerebral blood flowdetermined by[14C]iodoantiPsrine autoradiography Following middle cerebral artery occlusion[J].J Cereb Blood Flow Metab,1981,1(1):61-69.
[128]Ginsberg MD,Busto R.Rodent models of cerebralisehemia[J].Stroke,1989,20(12):1627-1642.
[129]Bederson JB,Pitts LH,Tsuji M,et al.Rat middle cerebral artery occlusion:Evaluation of the model and development of a neurologic examination[J].Stroke,1986,17(3):472 — 476.
[130]Tyson GW,Teasdale GM,Grallam DI,et al.Focal cerebral ischemia in the rat:Topography of hemodynamic and histopathologieal changes[J].Ann neurol,1984,15(6)559 — 567.
[131]Mohamed AA,Goloh O,Grallam DI,et al.Effect of pretreatmenit with the caleiuxnant agonist nimodiPineon local cerebral blood flow and histopathology after middle cerebral artery occludion[JI].AnnNeurol,1985,18(6):705 711.
[132]张玉林，程鸿，秦震．大鼠大脑中动脉阻断导致局灶脑梗塞[J]．上海医科大学学报，1990，17(8)：15—16．
[133]Wang LC,Futrell N,Wang DZ,et al.A reproducible model of middle cerebral infarcts,compatible with log-term survival,in aged rats[J].Stroke,1995,26(11):2087—2090.
[134]Kudo M,Aoyama A,Iehimori S,et al.An animal model of cerebral infarction-Homologous blood clot emboli in rats[J].Stroks,1982,13(4):505-508.
[135]Kaneko D,Nakamura N,Ogawa T.Cerebral infaretion in rats using homologous bloodemboli:development of a new experimental model[J].Stroke,1985,16(1):76-84.
[136]付蔓华，邹明辉，王玉升，等．花生四烯酸诱导大鼠急性脑缺血机理的实验研究[J]．中国病理生理学杂志，1991，7(3)：596，568．
[137]李威，李秋凤，苗利军，等．通腑化痰活血法对大鼠脑梗塞后血液流变学的影响[J]．中药药理与临床，1996，12(3)：3—6．
[138]Kuge Y,Minenatsu K,Yamaguehi T,et al.Nylon monofilament for intraluminal Middle cerebral artery oeecclusion in rats[J].Stroke,1995,26(9):1655 1658.
[139]Kameyama M,Suzuki J,Shirane R,Ogawa A.A new model of bilateral hemispheric Isehemia in the rat-three vessel occlusion model [J].stroke,1985,16(3):489-493.
[140]Longa EZ,Weinstein PR,Carlson S,et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20(1):84-91.
[141]刘运泉，戴颖．线栓法大鼠局灶性脑缺血模型的改进[J]．中国临床解剖学杂志，2005，23(2)：222-223．
[142]黄斌，王兴勇，匡凤梧，等．线栓法制备Wistar大鼠局灶性脑缺血模型的实验研究[J]．现代医药卫生，2005，21(15)：1935-1937．
[143]任建勋，刘俊，沈映君．线栓法建立大鼠局灶性脑缺血．模型方法的改进[J]．四川生理科学杂志，2005；27(2)：60-61．
[144]徐立新，袁芳．改良的大鼠脑局部缺血模型[J]．中国康复理论与实践，2005，11(1)：23-24．
[145]刘富东，许燕，杨倩．线栓法制作局灶性脑缺血再灌注动物模型的研究[J]．皖南医学院学报，2003，22(1)：22-24．
[146]田士强，王任直，李桂林，等．大鼠局灶性脑缺血模型的改进[J]．基础医学与临床，2004，24(4)：499-451．
[147]宋红松，樊东升，王荫华．血管内直接线栓闭塞法制备大鼠缺血性脑梗死模型[J]．中国康复理论与实践，2004，10(4)：245-246．
[148]郝玉曼，罗祖明，周东．局灶预缺血诱导脑缺血耐受的动物模型[J]．中风与神经疾病杂志，2003，20(2)：129-131．
[149]Watson BD,Dietrieh WD,Busto R,et al.Induction of reprodueible brain infaretion by photoehemically initiated thrombosis[J].Ann Neurol,1985,17(5):497-504.
[150]王伟，董为伟，傅雅各，等．光化学诱导鼠大脑中动脉闭塞及再通模型[J]．中国神经精神疾病杂志，1996，22(1)：27-30．
[151]Fuxe K,Kurosawa N,Cintra A,et al.Involvement of loeal isehemia inEndothelin-1 indueed lesions of theneostriatum of the anaesthetized rat[J].Exp Brain Res,1992,88(1):131-139.
[152]Levine S,Payan H.Effeets of ischemia and other Procedures on the brain and retina of the gerbil(Meriones unguieulatus)[J].Exp Neurol,1966,16(3):255-262.
[153]Levine S,Sohn D.Cerebral ischemia in infant and adult gerbils[J].Relation to incomplete circle of Willis.Arch Pathol,1969,87(3):315-317.
[154]Kahn K.The natural course of experimental cerebral infaretion in the gerbil[J].Neurology,1972,22(5):510-515.
[155]Harrison MJ,Browllbill D,Lewis PD,et al.Cerebral edema following carotid artery ligation in the gerbil[J].Arch Neurol, 1973，28(6)：389-391．
[156]郑骏年．细胞凋亡检测方法研究进展[J]．国外医学临床生物化学与检验学分册，1999，20(3)：124-126．
[2]周鸿雁，毛海峰，王一蓉，等．脑缺血损伤的研究进展[J]。湖南文理学院学报，2005，17(2)，72-75．
[3]张晓琴、章军建．神经病学．武汉大学出版社，2002，6：117-118．
[4]Chan PH.Reactive oxygen radicals in sigaling and damage in the ischemic brain[J].J Cereb Blood Flow Metab,2001,21(1):2-14.
[5]Lewen,Matz P,Chan PH.Free radical pathways in CNS injury [J].J Neurotrauma,2000,17(10):871-890.
[6]陈敏，李长清，胡长林，等．钙与脑缺血／再灌注后神经细胞凋亡[J]．脑与神经疾病杂志，2003，11(4)：253-255．
[7]Lewen A,Matz P,Chan PH.Free radical pathways in CNS injury [J].Neurotrauma,2000,17 (10) :871-890.
[8]Hignchi Y.increase in NO in the hypoxic-ischemic neonatalrat brain and supperession by 7-N1 and aminoguanidine[J].Eue J Pharmacol,1998,342(1):47-49.
[9]Kumura M,Inao S,Takayasu M,et al.Time course of expression of the three nitric oxide synthase isoforms after transient middle cerebral arteryocclusion in rats[J].Neurol Med Chir(Tokyo),2001,41(2):63-72.
[10]De Alba J,Cardenas A,Moro MA,et al.Down-regulation of neuronal nitric oxide synthase by nitric oxide after oxygen-glucose deprivation in rat forebrain slices[J].J Neurochem,1999,72(1):248-254.
[11]苏志达，李瑜，李宏建．卒中治疗药物临床前的实验研究[J]．国外医学脑血管疾病分册，2000，8(5)：290-293．
[12]高维娟．大鼠脑缺血再灌注后海马组织兴奋性氨基酸含量的动态观察．承德医学院学报，2003，20(3)：155—187．
[13]蔡竖平，桂秋萍，韩志涛，等．脑缺血-再灌注后海马迟发性神经元死亡的实验研究[J]．军医进修学院学报，2002，23(4)：268-270．
[14]张焰，陈群，顾卫东，等．灯盏花素对脑缺血再灌注沙土鼠兴奋性氨基酸释放 和学习记忆能力的影响[J]．中华实用中西医杂志，2004，4(17)：1930-1932．
[15]陈敏，李长清，胡长林，等．钙与脑缺血／再灌注后神经细胞凋亡[J]．脑与神经疾病杂志，2003，11(4)：253-25 5．
[16]Kinouchi H,Huang H,Arai S,et al.Induction of cyclooxygenase-2 messenger RNA after transient and permanent middle cerebral artery occlusion in rats:comparison with c-fos messenger RNA by using in situ hybridization [J].Neurosurg,1999,91 (6):1005-1012.
[17]VilanN,Castillo J,Davalos A,et al.Proinflammatory cytokines and early neurological Worsening in isehemic stroke.Stroke.2000,31(10):2325-2329.
[18]Stephenson D,Yin T,Smalstig EB,et al.Transcription factor Nuclear Factor Kappa B is activated in neurons after focal cerebral ischemia [J].Cere Blood flow Metab,2000,20 (3) :592- 603.
[19]冯春生，麻海春，岳云，等．异丙酚对大鼠局灶性脑缺血再灌注时核因子κB的活化和炎症因子表达的影响[J]．中华医学杂志，2004，84(24)：2110
[20]Clemens JA,Stephenson DT,Dixon EP,et al.Global cerebral ischemia activates nuclear factor-kappa B prior to evidence of DNA fragmentation [J].Mol Brain Res,1997,48 (2) :187-196.
[21]田代实， 王光海，郭国际．核因子κB在大鼠脑缺血耐受中的作用及其对细胞间黏附分子-1和Bcl-2表达的影响[J]．中风与神经疾病杂志，2004，21(3)：205-207．
[22]Nicolas B,Catherine W,Michel L,et al.Activation of the nuclear factor κB is a key event in brain tolerance [J].Neurosci.2001,21 (13) :4668-4677.
[23]Perkins ND.The Rel/ NF-kappa B family:friend and foe [J].Trends Biochem Sci,2000,25 (9) :434-440.
[24]Nogawa S,Zhang F,Ross ME,et al.Cyclooxygenase-2 gene expression in neurons contributes to ischemic brain damage [J].Neurosci,1997,17 (8) :2746-2755.
[25]Iadecola C,Forster C,Nogawa S,et al.Cyclooxygenase-2 immunoreactivity in the human brain following cerebral ischemia [J].Acta Neuropathol (Berl),1999,98 (1) :9-14.
[26]Kaufmann WE,W orley PF,Pegg J,et al.COX-2,a synaptically induced enzyme,is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex [J].Proc Natl Acad Sci USA,1996,93 (6) :2317-2321.
[27]李琴，张云，郭云良，等．肌苷对脑缺血再灌注后COX-2表达的调节作用[J]．中国老年医学杂志，2004，17(8)：640-711．
[28]Sasaki T,Kitagawa K,Yamagata K,et al.Amelioration of hippocampa neuronal damage after transient forebrain ischemia in cyclooxygenase-2 deficient mice [J].Cerebral Blood Flow Metab,2004,24 (1) :107-113.
[29]Kinoshita Y,Ueyama T,Senba E,et al.Expression of c-fos,heat shock protein 70,neurotrophins and cyclooxygenase-2 mRNA in response to focal cerebral ischemia/reperfusion in rats and their modification by magnesium sulfate [J].Neurotrauma,2001,18 (4) :435-445.
[30]Miettinen S,Fusco FR,Yrjanheikki J,et al.Spreading depression and focal brain ischemia induce cyclooxgenase-2 in cortical neurons through N-methyl-D-aspartic acid-receptors and phospholipase A2 [J].Proc Natl Acad Sci USA,1997,94 (12) :6500-6505.
[31]Mirjany M,Ho L,Pasinetti GM.Role of cyclooxygenase-2 in neuronal cellcycle activity and glutamate-mediated excitotoxicity [J].Pharmacol Exp Ther,2002,301 (2) :494-500.
[32]Nishikawa M,Stapleton PP,Freeman TA,et al.NS2398 inhibits tumor growth and liver metastasis of colon cancer through induction of apoptosis and suppression of the plasminogen activation system in a mouse model [J].Am Coll Surg,2004,199 (3) :428-435.
[33]Hunot S,Vila M,Teismann P,et al.JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease [J].PNAS,2004,101 (2):665-670.
[34]Sobel RA,Mitchell ME,Fonder G,Intercellular adhesion molecule (ICAM-1) in cellular immune reactions in the human central nervous system[J].Am-J-Pathol,1990,136 (6) :1309-1316.
[35]Chen CC,Rosenbloom CL,Imuro Y,et al.Ihibition of NF kappaB in activated rat hepatic stallate cells by proteasome inhibitors and an IkappaB super-repressor [J].Hepatology,1998,27 (5) :1285-95.
[36]Park,CW,Nico B,Trojano M,et al.High glucose-induced intercellular adhesion molecule (ICAM-1) expression through an osmotic effect in rat mesangial cells is PKC-NF-kappa B-dependent [J].Diabetologia,2000,43( 12):1544-1553.
[37]郝延磊，，蒲传强，张凤英，等．实验性脑缺血模型脑组织微血管细胞间粘附分子1表达的研究[J]．中华神经科杂志，1998，31(2)：105．
[38]郝延磊，蒲传强，朱克，等．细胞间粘附分子1和E选择素在局部脑缺血中的作用[J]．中华老年心脑血管病杂志，2000，2(1)：54-5 7．
[39]吴珊，董为伟，董佑忠．局灶脑缺血再灌流后ICAM-1表达于白细胞浸润[J]．中风与神经病杂志，2000，17(1)：5-7．
[40]叶诸榕．脑缺血的细胞死亡：坏死或凋亡．中华神经科杂志[J]，1998，31(5)：301-304．
[41]Wyllie A.H.,“Apoptosis(the 1992 Frank Rose Memorial Lecture)” ,Br J Cancer,1993,67 (2) :250-208.
[42]Arends M．J．，Wyllie A．H．，”Apoptosis：mechanisms and roles in pathology”，Int Rev Exp Pathol，1991，32：223-254．
[43]刘煜敏，徐仁，黄怀钧，等．兴奋性氨基酸、氧自由基与缺血再灌注损伤关系的实验观察[J]．卒中与神经疾病，2001，7(2)：98-100．
[44]Watson M,Yanlalllura HI,Roeske WR.A unique regulatory profile and regional distribution of pirenzepine binding in the rat provide evidence for distinct difference for apoptosis and necrosis[J].Life Sci,1983,32(4):3001-3011.
[45]Garcia JH,Ye ZR,Liu KE.Delayed neuronal death in experimental Ischemicstroke [M].In:ToUetal.eds:Maturation phenomenon in cerebral ischemia.Berlin:Springer-Verlag,2002,25(6):267-273.
[46]Harrison W,Beyaert R,Declercq W,Vandenabeele P.More than one way to die:apoptosis and necrosis and reactive oxygen damage[J].Onco gene,1999,18(54):7719-7730.
[47]Li Y,Chopp M,Powers C,et al.Apoptosis and protein expression after Foc 1 cerebral ischemia reperfussion in rats [J].Brain Res, 1997,765(2) :301.
[48]Hayashi Y,Tikhara I,Yagi T,et al. Immunohistochemical investigation of caspase-1 and effect of caspase-1 inhibitor in delayed neuronal death after transient cerebral ischemia[J]. BrainRes, 2001,893(2) : 113-120.
[49]Corman AM.Orreeniu S,Ceccatelli S.Apoptosis in neuronal cells:role of Caspase [J].Neuroreport, 1998,9:49-55.
[50]White BC,Sullivan JM, Degracia DJ, et al.Brain ischmia and reperfussion:molecular mechanisms of neuronal injury[J].J Neurol Sci, 2000,179(2) : 1-33.
[5l]Hartmann A,Hunot S,Michel PP.caspase-3:A vunerability factor and final effector in apoptotic death of dopeminergic neurons in Paekinson' sdisease[J].Proc Natl Acad SciUSA,2000,97 (6) :2875-2880.
[52]Harrison DC, Davis RP,Bond BC,et al. Caspase mRNA expression in ratmodel of focal cerebral ischemia reperfussion[J].Brain Res Mol, 2001,89(1):133-146.
[53] Sugawara T, Fujimura M, Morita-Fujimura Y, et al. Mitochondrial release of cytochrome c corresponds to the selective vulnerability of hippocampal CA1 neurons in rats after transient global cerebral ischemia [J]. Neurosci, 1999, 19(22): RC39.
[541 Antonawich FJ. Translocation of cytochrome c following transient global ischemia in the gerbil [J|. Neurosci Lett, 1999, 274 (2):123-126.
[55] Maeda K, Hata R, Gillardon F, et al.Aggeavation of brain injury after transiene focal ischemia in p53-deficient mice [J]. Brain Res Mol Brain Res, 2001, 88(1-2) : 54-61.
[56] GuptaS, Knowlton AA. HSP60, Bax, apoptosis and the heart [J]. Cell Mol Med,2005, 9(1): 51-58.
[57] Graham SH, Chen J, Clark RS. Bcl-2 family gene productd incerebral ischemia and traumatic brain injury [J]. Neurotrauma, 2000, 17 (10) : 831-841.
[58] Shimizu S, Nagayama T, Jin K.L, et al. Bcl-2 antisense treatment prevents induced of tolerance to focal ischemia in the rat brain [J]. Cereb Brain Flow Metab, 2001, 21 (3) : 233-243.
[59] Liu D, Lu C, Wan R, et al. Activation of mitochondria) APT-dependent potassium channels products neurons against ischemia-induced by a mechanism involve suppression of Bax translocation and cytochrome C release [J]. Cereb Blood Flow Metab, 2002, 22 (4) : 431-443.
[60] Takemoto O. Tomimoto H, Yanagihara T. Induction of c-fos and c-jun gene products and heat shock protein after brief and prolonged cerebral ischemia in gerbils [J]. Stroke, 1995, 26 (9) : 1639-1648.
[61] Dragunow M, Beilharz E, Sirimanne E, et al. Immediate early gene protein expression in neurons undergoing delayed death, but not necrosis, following hypoxic ischemic injury to the young rat brain [J]. Brain Res Mol Brain Res,1994, 25 ( 1—2) : 19-33.
[62] Whitfield J, Neame SJ, Paquet L, et al. Dominant-negative c-Jun promotes neuronal survival by reducing B I M expression and inhibiting mitochondrial cytochrome c release [J]. Neuron, 2001, 29 (3) : 629-643.
[80] Li Y, Chopp M, Power C, et al. Apoptosis and protein expression after focal cerebral ischemia in rat[J]. Brain Res, 1997, 15: 301.
[81] Maeda K, Hata R, Gillardon F, et al. Aggravation of brain injury after transient focal ischemia in p53-deficient mice [J]. Mol Brain Res, 2001,88: 54-61.
[82] Looderen V, Campagne M, GilL R. Cell cycle-related gene expression in the adult rat brain selective induction of cyclin G1 and p21 WAFI/CIPI in neurons following focal cerebral ischemia [J]. Neuroscience, 1998, 84: 1097.
[83] Miyashiton T, Harigai M, Hanada Metal. Identification of a p53-dependent negative response element in the bcl-2 gene[J]. Cancer Res, 1994, 54: 3131.
[85] Min H J , Tomohori Kaku, Junichi Hada, el al. Different effects of eNOS and nNOS inhibition on transient forebrain ischemia [J]. Brain Res, 2002, 946 :139-142.
[86]Vaughan CJ ,Delanty N ,Basson CT.Statin therapy and stroke Prevention[J].CurrOpin Carrdiol,2001,(4):219—228.
[87]Oconnell AW ,Fox GB ,Kjoiler C ,el al.Antiischemic and cognition-enhancing properties of NNC-711.agamma-arninbutyricacid reccptakeinhibitor [J].Eur J Pharmacol,2001,424(1):37—43.
[88]Eguchik,Kariok.Shimada K Beneficial effect of ARB of ischemic stroke [J].Nippon Rinsho ,2002,60(10) :1987— 1998.
[89]Ferrer I,Planas AM.Signaling of cell death and cell survial following focal cerebral ischemia:life and death struggle in the penumbra[J].J Neuropathol Exp Neurol,2003,62(4):329-339.
[90]DuG,Zhang J.Protective effects of salvianolic acid A against impairment of Memory induced by cerebral isehemia-reperfusion in miee.Chin Med J(Engl).1997,110(1):65-68.
[91]Li l.Protective effects of schisanhenol,salvianolic aeid A and SY-L on oxidative Stress induced injuries of cerebral cells and their mechanisms.Sheng Li Ke Xue Jin Zhan.1998,29(1) :35-8.
[92]Yagi A,et al.Chem,Pharm Bull.1977,25(7):1770.
[93]万金志．芦荟的化学成分及其研究．中草药，1999，30(2)：151．
[94]Bill H,Meanalley.US,5:468,737.
[95]An Susun,etc.Sci.conf.Asian Soc.Cosmet.Sci3rd.1997:70-73.
[96]Heggers John P,etc.Phytother.Res,1995,9(6) :455-457.
[97]Kenshi Fukuyasu,etc.Fragrance[J].1995,23(8) :82-85.
[98]W.Olechnowiez-Stepien,etc.HerbaPol.1988,34(1) :35-42.
[99]Shihokokaku.etc.Biosei,Bioteehnol,Bioehem.1997,61 (3) :558-560.
[100]冈田和也．日癌疗治．1994，29(8)：1191．
[101]李伟芳．中国中药杂志．1991，16(11)：688．
[102]王官．福建中医．1991，22(1)：44-45．
[103]王宝成．人民军医．1996，4：40．
[104]Yushi Sato，etc．(日本)药学杂志．1990，110(11)：876-884．
[105]Hlroshi Hikino，etc．(日本)药学杂志 0553．1989，109(5)：335-339．
[106]邓小云，丁登峰，戴美红，等．植物多糖药理作用研究进展．中医药导报，2006， 12(9):86-88.
[107]Roberts DB,Travis EL.Acemannan-containing wound dressing gel reduces Radiation-induced skin reactions in C3H mice[J].Int J Radiat Oneol Biol Phys,1995,32(4):1047-1052.
[108]Kahion JB,Kem PMC,Carpenter PH,et al.Inhibition of AIDS virus replication by acemannan in vitro[J].Mol Biother.1991,3(3):127-135.
[109]Montaner JS,Gill J,Singer J,et al.Double-blind placebo-controlled pilot trial of acemannan in advanced human inununodeficiency virus disease[J].J Acquir Immune DefiC Syndr Hum Retrovirol.1996 ,12(2):153-157.
[110]Thomas DR,Goode PS,LaMaster K,et al.Acemannan hydrogel dressing versus saline Dressing for pressure uleers.A randomized,controlled trial[J].Adv Wound Care,1998,11(6):273-276.
[111]Saito H,Imanishi K,Okabe S.EffeCts of aloe extracts,aloctin A,on gastric secretion and on experimental gastric lesions in rats[J].Yakugaku Zasshi,1989,109(5):335-339.
[112]信照亮．鼠急性脑缺血的实验研究进展[J]．国外医学神经病学神经外科学分册，1991，18(2)：90-93．
[113]陈春富．大鼠局灶性脑缺血模型研究进展[J]．国外医学脑血管病分册，1995，3(5)：227-230．
[114]ponien U,Rateheson RA,Salford LG Optimal freezing conditions forcerebral Metabolites in rats[J].Neuxochem,1973,21(5):1127-1138.
[115]Eklof B,siesjo BK.The effct of bilateral earotid artery ligation on the blood flow and energy state of the rat brain[J].Aeta Physiol Seand,1972,86(2):155-165.
[116]Eklof B,Siesjo BK.Cerebral blood flow in isehemia eaused by carotid artery ligation in the rat[J].Aeta Physiol Seand,1973,87(1):69-77.
[117]Nordstrom GH ,SiesjoBK Effcts of Phenobarbital in cerebral isehemia[J].PartⅠ：Stroke,1978,9(4)：327-335.
[118]王蕊，杨秦飞，唐一鹏，等．大鼠拟血管性痴呆模型的建立及中药9602防治作用初探[J]．北京中医药大学学报，2000，23(5)：30-30．
[119]傅建华，杜贵友．天麻促智颗粒对反复脑缺血再灌小鼠脑组织递质性氨基酸含量的影响[J]．中国中药杂志，2001，26(1)：53-55．
[120]任德成，杜冠华，张均田．总丹酚酸对脑缺血再灌注损伤的保护作用[J]．中国药理学通报，2002，18(3)：275-277．
[121]Pulsineli WA,Brieley JB.A new model of bilateral hemispheric isehemia in the Unanesthetized rat[J].Stroke,1979,10(3):267-272.
[122]Maerae I M.New models of foeal cerebral ischemia[J].Br J Clin Pharmaeol,1992,34(4):302-308.
[123]Kameyama M,Suzuki J,Shirane R,et al.A new model of bilateral hemispheric isehemia in the rat-three vessel occlusion model[J].Stroke,1985,16(3):489-493.
[124]李威，范军铭，贾士奇，等．电针对大鼠全脑缺血再灌流损伤的保护作用[J]．中国针灸，1996，36(11)：211-213．
[125]王军，马开，屠万倩．电针对全脑缺血再灌流大鼠脑组织氨基酸递质的影响[J]．辽宁中医杂志，2007，34(2)：226-225．
[126]Tamura A,Graham D1,McCulloch J,et al.Foeal cerebral isehemia in the rat:1.DeseriPtion of teehnique and early neuroPathologieal consequences following middle Cerebral artery occalusion[J].J Cerb Blood Flow Metab,1981,1(1):53-60.
[127]TAmura.A,Graham DI,McCulloeh J,et al.Foeal cerebral isehaemia in the rat:2.Regional cerebral blood flowdetermined by[14C]iodoantiPsrine autoradiography Following middle cerebral artery occlusion[J].J Cereb Blood Flow Metab,1981,1(1):61-69.
[128]Ginsberg MD,Busto R.Rodent models of cerebralisehemia[J].Stroke,1989,20(12):1627-1642.
[129]Bederson JB,Pitts LH,Tsuji M,et al.Rat middle cerebral artery occlusion:Evaluation of the model and development of a neurologic examination[J].Stroke,1986,17(3):472 — 476.
[130]Tyson GW,Teasdale GM,Grallam DI,et al.Focal cerebral ischemia in the rat:Topography of hemodynamic and histopathologieal changes[J].Ann neurol,1984,15(6)559 — 567.
[131]Mohamed AA,Goloh O,Grallam DI,et al.Effect of pretreatmenit with the caleiuxnant agonist nimodiPineon local cerebral blood flow and histopathology after middle cerebral artery occludion[JI].AnnNeurol,1985,18(6):705 711.
[132]张玉林，程鸿，秦震．大鼠大脑中动脉阻断导致局灶脑梗塞[J]．上海医科大学学报，1990，17(8)：15—16．
[133]Wang LC,Futrell N,Wang DZ,et al.A reproducible model of middle cerebral infarcts,compatible with log-term survival,in aged rats[J].Stroke,1995,26(11):2087—2090.
[134]Kudo M,Aoyama A,Iehimori S,et al.An animal model of cerebral infarction-Homologous blood clot emboli in rats[J].Stroks,1982,13(4):505-508.
[135]Kaneko D,Nakamura N,Ogawa T.Cerebral infaretion in rats using homologous bloodemboli:development of a new experimental model[J].Stroke,1985,16(1):76-84.
[136]付蔓华，邹明辉，王玉升，等．花生四烯酸诱导大鼠急性脑缺血机理的实验研究[J]．中国病理生理学杂志，1991，7(3)：596，568．
[137]李威，李秋凤，苗利军，等．通腑化痰活血法对大鼠脑梗塞后血液流变学的影响[J]．中药药理与临床，1996，12(3)：3—6．
[138]Kuge Y,Minenatsu K,Yamaguehi T,et al.Nylon monofilament for intraluminal Middle cerebral artery oeecclusion in rats[J].Stroke,1995,26(9):1655 1658.
[139]Kameyama M,Suzuki J,Shirane R,Ogawa A.A new model of bilateral hemispheric Isehemia in the rat-three vessel occlusion model [J].stroke,1985,16(3):489-493.
[140]Longa EZ,Weinstein PR,Carlson S,et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20(1):84-91.
[141]刘运泉，戴颖．线栓法大鼠局灶性脑缺血模型的改进[J]．中国临床解剖学杂志，2005，23(2)：222-223．
[142]黄斌，王兴勇，匡凤梧，等．线栓法制备Wistar大鼠局灶性脑缺血模型的实验研究[J]．现代医药卫生，2005，21(15)：1935-1937．
[143]任建勋，刘俊，沈映君．线栓法建立大鼠局灶性脑缺血．模型方法的改进[J]．四川生理科学杂志，2005；27(2)：60-61．
[144]徐立新，袁芳．改良的大鼠脑局部缺血模型[J]．中国康复理论与实践，2005，11(1)：23-24．
[145]刘富东，许燕，杨倩．线栓法制作局灶性脑缺血再灌注动物模型的研究[J]．皖南医学院学报，2003，22(1)：22-24．
[146]田士强，王任直，李桂林，等．大鼠局灶性脑缺血模型的改进[J]．基础医学与临床，2004，24(4)：499-451．
[147]宋红松，樊东升，王荫华．血管内直接线栓闭塞法制备大鼠缺血性脑梗死模型[J]．中国康复理论与实践，2004，10(4)：245-246．
[148]郝玉曼，罗祖明，周东．局灶预缺血诱导脑缺血耐受的动物模型[J]．中风与神经疾病杂志，2003，20(2)：129-131．
[149]Watson BD,Dietrieh WD,Busto R,et al.Induction of reprodueible brain infaretion by photoehemically initiated thrombosis[J].Ann Neurol,1985,17(5):497-504.
[150]王伟，董为伟，傅雅各，等．光化学诱导鼠大脑中动脉闭塞及再通模型[J]．中国神经精神疾病杂志，1996，22(1)：27-30．
[151]Fuxe K,Kurosawa N,Cintra A,et al.Involvement of loeal isehemia inEndothelin-1 indueed lesions of theneostriatum of the anaesthetized rat[J].Exp Brain Res,1992,88(1):131-139.
[152]Levine S,Payan H.Effeets of ischemia and other Procedures on the brain and retina of the gerbil(Meriones unguieulatus)[J].Exp Neurol,1966,16(3):255-262.
[153]Levine S,Sohn D.Cerebral ischemia in infant and adult gerbils[J].Relation to incomplete circle of Willis.Arch Pathol,1969,87(3):315-317.
[154]Kahn K.The natural course of experimental cerebral infaretion in the gerbil[J].Neurology,1972,22(5):510-515.
[155]Harrison MJ,Browllbill D,Lewis PD,et al.Cerebral edema following carotid artery ligation in the gerbil[J].Arch Neurol, 1973，28(6)：389-391．
[156]郑骏年．细胞凋亡检测方法研究进展[J]．国外医学临床生物化学与检验学分册，1999，20(3)：124-126．
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