一氧化碳对体外培养少突胶质细胞Nogo-A的影响
|
摘要
研究背景和目的:急性一氧化碳中毒(acute carbon monoxide poisoning,ACMP)是较常见的职业性及生活性中毒,可造成中枢神经系统(centeral neverous system,CNS)损伤。部分患者急性中毒症状消失以后,经过数天或数周表现正常或接近正常的假愈期,会出现以痴呆为主的精神神经症状称为急性一氧化碳中毒迟发性脑病( delayed encephalopathy after acute carbon monoxide poisoning,DEACMP),DEACMP患者颅脑影像学上白质脱髓鞘显著[1-4]。假愈期的存在给DEACMP的早期诊断带来困难,给有效防治带来困难,给社会家庭造成很大负担。Nogo-A蛋白是神经元轴突生长抑制因子之一,主要表达于CNS的少突胶质细胞[5],已证实Nogo-A可触发神经元轴突抑制、生长锥崩溃、阻止神经纤维散布,其受体(Nogo- receptor ,NgR)广泛分布于多种神经元,还存在于胶质细胞间隙缝连接处,提示NgR可通过隙缝连接来调节胶质细胞间的联系,但少突胶质细胞本身无NgR分布[6]。这些使得Nogo-A及NgR成为限制神经再生和轴突损伤修复的关键因素[7]。Nogo-A是否参与了ACMP脑损害、DEACMP的发病机制尚未见报道。鉴于Nogo-A蛋白及NgR的分布特点,及DEACMP患者颅脑影像学上白质脱髓鞘突出,我们推测Nogo-A蛋白及NgR与ACMP脑损害,尤其与DEACMP关系密切。内源性CO是重要的气信使分子之一,具有传递细胞间信息、调节细胞功能的作用[8],CO由血红素氧合酶(hemeoxygenease,HO)代谢产生的,HO抑制剂锌原卟啉-9(Zinc Porphyrin IX,ZnPPIX)可抑制CO生成,已用于研究内源性CO的神经内分泌调节作用[8]。作为体内合成内源性CO的唯一酶系统,HO-CO系统日益受到关注,其对Nogo-A及NgR的影响目前亦未见报道。本实验中,排除缺氧影响,我们用外源性CO直接处理体外培养少突胶质细胞,并用ZnPPIX抑制了HO活性,观察少突胶质细胞Nogo-A在mRNA及蛋白质水平的表达情况,以期探讨Nogo-A在ACMP脑损害和DEACMP中可能存在的病理生理机制,为研究ACMP脑损害和DEACMP的发病机制和治疗方面提供一个新的实验依据。
方法:(1)取新生2天SD大鼠的视神经,采用组织块培养法,用DMEM/F12化学限定培养液培养、纯化少突胶质细胞。细胞免疫化学检测少突胶质细胞髓鞘碱性蛋白(Myelin basic protein,MBP)表达,鉴定少突胶质细胞,并计算阳性率。(2)在排除缺氧的影响下,1%CO处理少突胶质细胞,采用RT-PCR及细胞免疫组化观察6h、24h、48h少突胶质细胞Nogo-AmRNA及其蛋白表达。(3)取Nogo-AmRNA表达最高的时间点,预先加入ZNPP-IX抑制HO活性,1%CO处理少突胶质细胞,检测Nogo-AmRNA及其蛋白。
结果:1、组织块24h开始贴壁,48h-72h可见神经组织边缘游出少量细胞,主要为圆形。9-10d左右细胞基本从组织块中游离出来,平铺于皿底。11d左右获得的细胞胞体基本为呈圆形或多角形,直径约6-10μm,细胞核较大,胞质少,突起丰富,交织成网。细胞细胞免疫化学染色MBP蛋白阳性,95%以上为阳性细胞。2、RT-PCR检测Nogo-AmRNA表达;(1)对照组:6h、24h、48h均有Nogo-A mRNA表达分别为:0.733±0.034、0.705±0.027、0.717±0.04,且未见其表达随时间发生明显变化;CO组:6h、24h、48h Nogo-AmRNA表达分别为: 1.042±0.015、1.304±0.008、0.937±0.005,与对照组相比有统计学差异(P<0.05)。(2)ZNPP-IX组与单纯CO处理组( COZN)相比Nogo-AmRNA增加,值为: 1.454±0.041、1.278±0.032,(P<0.01),有统计学差异。3、细胞免疫化学检测Nogo-A蛋白表达:Nogo-A表达于少突胶质细胞的胞膜和胞浆中,为棕褐色。免疫细胞化学染色图像分析结果显示:(1)Control组6h、24h、48h均有Nogo-A蛋白表达,未见其表达随时间发生明显变化,累计光密度值为:2836.74±94.30;2761.16±75.80 ; 2780.16±95.46 ; CO组6h、24h、48h累计光密度值为:4087.20±79.28;7240.40±63.25;3449.90±93.46;CO组各时间点累计光密度值与Control组相比有统计学差异(P<0.05)(3)ZNPP-IX组:ZNPP-IX干预后与单纯CO处理组(COZN)相比Nogo-A蛋白表达增加,有统计学差异(P<0.05),累计光密度值分别为:7159.41±97.32;9880.76±105.81。
结论:(1)在排除缺氧的影响下,外源性CO诱导体外培养少突胶质细胞Nogo-A mRNA及蛋白表达增加。(2)在排除缺氧的影响下,外源性CO诱导体外培养少突胶质细胞Nogo-A mRNA表达增加时,HO-CO系统对Nogo-A mRNA及蛋白表达有抑制作用。
Background and purpose: Acute carbon monoxide poisoning (ACMP) is the common occupational poison in our life.It can cause the injury of central nervous system (CNS).After acute poisoning symptoms disappeared , some patients will present normal or near normal for a few days or weeks ,It called the false period.Then They present mainly the dementia symptoms ,which known as the delayed encephalopathy after acute carbon monoxide poisoning, DEACMP, Brain MRI of patients with DEACMP ,the white matter is demyelinating significantly[1-4]. Because of the false period, it is difficult to diagnose DEACMP in forepart accurately. It is difficult to effectively prevent and control, and bring a great burden on the family which has the patient. Nogo-A is one of the nervous growth inhibitors in CNS.It mainly expressed by oligodendrocytes which are in the CNS[5].It has been confirmed that Nogo-A can trigger the growth cone collapse , inhibite the regrowth of nerve axons,and block prevent the Spread of the nerve fibers , and its receptor (NgR) widely distributes in lots of neurons,which immune electron microscopy studies show that NgR has immune response to glial cells and also exist in the seam connection in glial cells, NgR which is in the seam connection between the glial cells may regulate their signal transmit,but there is no NgR in oligodendrocytses[6].All those make Nogo-A and it’s receptors become the key factor to restricte the regrowth of nerve axons and prevent the regeneration of CNS from it’s injury [7] .whether Nogo-A was involved in the ACMP’s brain damage and DEACMP the mechanism or not ,which has not been reported. In view of the distribution of Nogo-A and its receptors, also the white matter demyelinated prominently on DEACMP patients’s brain MRI, we speculate that Nogo-A and it’s receptor system have some contributions to the ACMP, especially to the DEACMP. Endogenous CO is one of the important elements of the air courier. It can transfer the information between cells and regulating the function of cells . CO mainly produce by the metabolism of the Heme oxygenase ( HO).Zinc Porphyrin IX (ZnPPIX) is the inhibitor of HO, it can inhibit the produce of endogenous CO, and it has been used to study the neuroendocrine regulator function of the endogenous CO[8]. As the only one system of synthesizing endogenous CO,the HO-CO system has been pay more attention.In addition, CO as a gas messenger molecules in brain, its relationship whit Nogo-A and NgR also has not been reported in the present. In our study, after excluding the effect of hypoxia,we treat oligodendrocytes with 1%CO directly, at the same time we use ZnPPIX inhibit the produce of the endogenous CO ,and then observed the expression of Nogo-AmRNA and its protein. In order to discusss the potential pathophysiological function of Nogo-A and the HO-CO system in ACMP and DEACMP, and provid a new experimental clue for studying the pathogenesis and treatment of ACMP and DEACMP.
Methods: (1) The optic nerves of 2 days’newborn SD rats.Optic nerve tissues were cultured directly and DMEM/F12 chemically defined culture medium was used to culture and purify oligodendrocytes. We detect the expression of the myelin basic protein (MBP) in oligodendrocytses by immunocytochemical examination.(2) Excluding the effect of hypoxia, we treat oligodendrocytes with 1% CO directly, and detect the expression of Nogo-A mRNA and Nogo-A protein of 6h, 24h, 48h by RT-PCR and immunohistochemical. (3) Select the time when the Nogo-A mRNA express into the peak value, and pre-add ZNPP-IX in medium in order to inhibit the produce of endogenous CO, detect the expression of Nogo-A mRNA and protein by RT-PCR and immunohistochemical.
Results: 1、After 24 hours,tissue is adherenting to Petri dish,After 48-72hours ,the edge of the nerve tissue has a small number of rotundate and cells travelling out. About 9-10 days later all the cells of optic nerves can almostly traveled out and overspread the dish. In the 11days, the cells growth into a round and polygonal shape, the diameter is about 6-10um. The cells have larger nuclei and less cytoplasm. We bserved more than 95 percent cells are positive by immunocytochemical examination.2、Detect the expression of Nogo-AmRNA by RT-PCR:(1) The expression of Nogo-A mRNA of the control group (control): 6h, 24h, 48h are:0.733±0.034, 0.705±0.027,0.717±0.04, and there is no significantly change; the expression of Nogo-AmRNA of the CO treated group compared with the control group has increased at each time point: 6 h (1.042±0.015 vs 0.733±0.034, P <0.05); 24h (1.304±0.008 vs 0.705±0.027,P <0.05);48h (0.937±0.005 vs 0.717±0.04, P <0.05)。(2) The ZNPP-IX group compared with COZN,the expression of Nogo-AmRNA has significantly increased(1.454±0.041 vs 1.278±0.032, P <0.01). 3、The expression of Nogo-A protein of each group has the same changes with the expression of Nogo-AmRNA. The Cumulative optical density of each group the control group 6h, 24h, 48h are 2836.74±94.30,2761.16±75.80,2780.16±95.46;the CO group 6h,24h,48h are4087.20±79.28,7240.40±63.25,3449.90±93.4,compared with the control group has significantly change(P<0.05);the ZNPP-IX group is 9880.76±105.81, compared with the COZN group has significantly change(P<0.05)。
Conclusion: (1) Excluding the influence of hypoxia,exogenous CO can increase the expression of Nogo-A mRNA and its protein of oligodendrocytes which is cultured in vitro.(2)Excluding the influence of hypoxiawhen exogenous CO increases the expression of Nogo-A mRNA and its protein of oligodendrocytes,the HO-CO system can inhibit the expression of Nogo-A mRNA and its protein.
方法:(1)取新生2天SD大鼠的视神经,采用组织块培养法,用DMEM/F12化学限定培养液培养、纯化少突胶质细胞。细胞免疫化学检测少突胶质细胞髓鞘碱性蛋白(Myelin basic protein,MBP)表达,鉴定少突胶质细胞,并计算阳性率。(2)在排除缺氧的影响下,1%CO处理少突胶质细胞,采用RT-PCR及细胞免疫组化观察6h、24h、48h少突胶质细胞Nogo-AmRNA及其蛋白表达。(3)取Nogo-AmRNA表达最高的时间点,预先加入ZNPP-IX抑制HO活性,1%CO处理少突胶质细胞,检测Nogo-AmRNA及其蛋白。
结果:1、组织块24h开始贴壁,48h-72h可见神经组织边缘游出少量细胞,主要为圆形。9-10d左右细胞基本从组织块中游离出来,平铺于皿底。11d左右获得的细胞胞体基本为呈圆形或多角形,直径约6-10μm,细胞核较大,胞质少,突起丰富,交织成网。细胞细胞免疫化学染色MBP蛋白阳性,95%以上为阳性细胞。2、RT-PCR检测Nogo-AmRNA表达;(1)对照组:6h、24h、48h均有Nogo-A mRNA表达分别为:0.733±0.034、0.705±0.027、0.717±0.04,且未见其表达随时间发生明显变化;CO组:6h、24h、48h Nogo-AmRNA表达分别为: 1.042±0.015、1.304±0.008、0.937±0.005,与对照组相比有统计学差异(P<0.05)。(2)ZNPP-IX组与单纯CO处理组( COZN)相比Nogo-AmRNA增加,值为: 1.454±0.041、1.278±0.032,(P<0.01),有统计学差异。3、细胞免疫化学检测Nogo-A蛋白表达:Nogo-A表达于少突胶质细胞的胞膜和胞浆中,为棕褐色。免疫细胞化学染色图像分析结果显示:(1)Control组6h、24h、48h均有Nogo-A蛋白表达,未见其表达随时间发生明显变化,累计光密度值为:2836.74±94.30;2761.16±75.80 ; 2780.16±95.46 ; CO组6h、24h、48h累计光密度值为:4087.20±79.28;7240.40±63.25;3449.90±93.46;CO组各时间点累计光密度值与Control组相比有统计学差异(P<0.05)(3)ZNPP-IX组:ZNPP-IX干预后与单纯CO处理组(COZN)相比Nogo-A蛋白表达增加,有统计学差异(P<0.05),累计光密度值分别为:7159.41±97.32;9880.76±105.81。
结论:(1)在排除缺氧的影响下,外源性CO诱导体外培养少突胶质细胞Nogo-A mRNA及蛋白表达增加。(2)在排除缺氧的影响下,外源性CO诱导体外培养少突胶质细胞Nogo-A mRNA表达增加时,HO-CO系统对Nogo-A mRNA及蛋白表达有抑制作用。
Background and purpose: Acute carbon monoxide poisoning (ACMP) is the common occupational poison in our life.It can cause the injury of central nervous system (CNS).After acute poisoning symptoms disappeared , some patients will present normal or near normal for a few days or weeks ,It called the false period.Then They present mainly the dementia symptoms ,which known as the delayed encephalopathy after acute carbon monoxide poisoning, DEACMP, Brain MRI of patients with DEACMP ,the white matter is demyelinating significantly[1-4]. Because of the false period, it is difficult to diagnose DEACMP in forepart accurately. It is difficult to effectively prevent and control, and bring a great burden on the family which has the patient. Nogo-A is one of the nervous growth inhibitors in CNS.It mainly expressed by oligodendrocytes which are in the CNS[5].It has been confirmed that Nogo-A can trigger the growth cone collapse , inhibite the regrowth of nerve axons,and block prevent the Spread of the nerve fibers , and its receptor (NgR) widely distributes in lots of neurons,which immune electron microscopy studies show that NgR has immune response to glial cells and also exist in the seam connection in glial cells, NgR which is in the seam connection between the glial cells may regulate their signal transmit,but there is no NgR in oligodendrocytses[6].All those make Nogo-A and it’s receptors become the key factor to restricte the regrowth of nerve axons and prevent the regeneration of CNS from it’s injury [7] .whether Nogo-A was involved in the ACMP’s brain damage and DEACMP the mechanism or not ,which has not been reported. In view of the distribution of Nogo-A and its receptors, also the white matter demyelinated prominently on DEACMP patients’s brain MRI, we speculate that Nogo-A and it’s receptor system have some contributions to the ACMP, especially to the DEACMP. Endogenous CO is one of the important elements of the air courier. It can transfer the information between cells and regulating the function of cells . CO mainly produce by the metabolism of the Heme oxygenase ( HO).Zinc Porphyrin IX (ZnPPIX) is the inhibitor of HO, it can inhibit the produce of endogenous CO, and it has been used to study the neuroendocrine regulator function of the endogenous CO[8]. As the only one system of synthesizing endogenous CO,the HO-CO system has been pay more attention.In addition, CO as a gas messenger molecules in brain, its relationship whit Nogo-A and NgR also has not been reported in the present. In our study, after excluding the effect of hypoxia,we treat oligodendrocytes with 1%CO directly, at the same time we use ZnPPIX inhibit the produce of the endogenous CO ,and then observed the expression of Nogo-AmRNA and its protein. In order to discusss the potential pathophysiological function of Nogo-A and the HO-CO system in ACMP and DEACMP, and provid a new experimental clue for studying the pathogenesis and treatment of ACMP and DEACMP.
Methods: (1) The optic nerves of 2 days’newborn SD rats.Optic nerve tissues were cultured directly and DMEM/F12 chemically defined culture medium was used to culture and purify oligodendrocytes. We detect the expression of the myelin basic protein (MBP) in oligodendrocytses by immunocytochemical examination.(2) Excluding the effect of hypoxia, we treat oligodendrocytes with 1% CO directly, and detect the expression of Nogo-A mRNA and Nogo-A protein of 6h, 24h, 48h by RT-PCR and immunohistochemical. (3) Select the time when the Nogo-A mRNA express into the peak value, and pre-add ZNPP-IX in medium in order to inhibit the produce of endogenous CO, detect the expression of Nogo-A mRNA and protein by RT-PCR and immunohistochemical.
Results: 1、After 24 hours,tissue is adherenting to Petri dish,After 48-72hours ,the edge of the nerve tissue has a small number of rotundate and cells travelling out. About 9-10 days later all the cells of optic nerves can almostly traveled out and overspread the dish. In the 11days, the cells growth into a round and polygonal shape, the diameter is about 6-10um. The cells have larger nuclei and less cytoplasm. We bserved more than 95 percent cells are positive by immunocytochemical examination.2、Detect the expression of Nogo-AmRNA by RT-PCR:(1) The expression of Nogo-A mRNA of the control group (control): 6h, 24h, 48h are:0.733±0.034, 0.705±0.027,0.717±0.04, and there is no significantly change; the expression of Nogo-AmRNA of the CO treated group compared with the control group has increased at each time point: 6 h (1.042±0.015 vs 0.733±0.034, P <0.05); 24h (1.304±0.008 vs 0.705±0.027,P <0.05);48h (0.937±0.005 vs 0.717±0.04, P <0.05)。(2) The ZNPP-IX group compared with COZN,the expression of Nogo-AmRNA has significantly increased(1.454±0.041 vs 1.278±0.032, P <0.01). 3、The expression of Nogo-A protein of each group has the same changes with the expression of Nogo-AmRNA. The Cumulative optical density of each group the control group 6h, 24h, 48h are 2836.74±94.30,2761.16±75.80,2780.16±95.46;the CO group 6h,24h,48h are4087.20±79.28,7240.40±63.25,3449.90±93.4,compared with the control group has significantly change(P<0.05);the ZNPP-IX group is 9880.76±105.81, compared with the COZN group has significantly change(P<0.05)。
Conclusion: (1) Excluding the influence of hypoxia,exogenous CO can increase the expression of Nogo-A mRNA and its protein of oligodendrocytes which is cultured in vitro.(2)Excluding the influence of hypoxiawhen exogenous CO increases the expression of Nogo-A mRNA and its protein of oligodendrocytes,the HO-CO system can inhibit the expression of Nogo-A mRNA and its protein.
引文
1. WalkerE,HayA.carbon monoxide poisoning .[J].Brit Med J.1999.319;1082-1083
2. Mathieu D,Matlueunoif M,Wathlel F.CO poisoning present aspects.[J].Bulletin del academie Nationale Medicine,1996,180(5):965-973.
3.何风生.中华职业医学.[M].北京:人民卫生出版社.1999:424-431.
4. MiroO. Casademont J. barrientos.et al.Mitochondrial cytochrome coxidase inhibiting during acute carbon monoxide poisoning[J].Pharm toxicol.1998.82:199-202
5. Jin WI,Iiu YY,Liu HL,et a1.Intraneuronal location of Nogo-A in the Rat.[J].J Comp Neurol,2003,458:l-10.
6. Liu X,Liu YY,Jin wL,et a1.Nogo-66 receptor at cerebellar cortical glia gap junctions in the rat1[J].Neurosignals,2005,14(3):96.
7. Oertle T,Marjan E.Nogo-A Inhihits Neurite Outgrowth and Cell Spreading with Three Discrete Regions.[J].Neuroscience.2003,23(13):5393-5406.
8. Pozzoli G,MancusoC,Mirtella A,et a1.Carbon monoxide as a novel neuroendocrine modulator inhibition of stimulated corticotropinreleasing hormone release from acute rat hypothalamic explants . [J] . Endocrinology , 1994 , 135(6) : 2314-2317.
9. Chen MS,Huber AB,van der Haar ME.et a1.Nogo-A is a myelin associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1 . [J] . Nature , 2000(6768),403:434-439.
10. Abraham N G,Kappas 18 A.Heme oxygenase and the cardiovascular renal system. [J].Free Radio Biol Med,2005,39(1):1-25.
11. Meyer J.Comparison of carbon monoxide,nitric oxide,and nitrite as inhibitors of the nitrogenase from Clostridiumpasteurianum.Arch Biochem Biophys 1981;210:246-256.
12. Shibahara S,Yoshizawa M ,Suzuki H,Takeda K,Meguro K,EndoK.Functional analysis of eDNA for two types of human heme oxygenase and evidence for their separate regulation.[J].Bioc hem 1993;1 13:214-218.
13. McCoubreyW K,HuangTJ.MainesMD.Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3.Eur J Biochem 1997;247:725-732
14. Wen-Xing YANG,Qi-Lan ZHANG,Hai-Yan HU,.Involvement of endogenous carbon monoxide in regulation of respiratory rhythmin vitro. Acta Physiologica Sinica,June 25.2007,59(3):325-330
15. Mancuse C.Heme oxygenase and it sproduct s in the nervous system.[J].Antioxid Redox Signal,2004,6(5):878-887.
16. Bidmon HJ,Emde B,Oermann E,et a1.Heine oxygenase-l (HSP-32) and hemeoxygenase-2 inductioninn Lronsand glial cells of cerebral regions and its relation to iron accumulation after focal cortical photothrombosis.[J]Exp Neurol,2001,168(1):l-22
17. SehipperHM.Heme oxygenase-l:a role in brain aging and neurodegeneration[J].Exp Gerontol,2000,35(6-7):821-830.
18. Acquaviva R,Campisi A,Raciti G,et a1.Propofol inhibits caspase-3 in astroglial cells:role of heme oxygenase-1.[J].Curr Neurovase Res,2005,2(2):141-148.
19. Volti GL,Sacerdoti D,sangras B,el a1.Carbon monoxide signaling in promoting angiogenesis in human microvessel endothelial cells.[J].Antioxid Redox Signal, 2005,7(56):704-710.
20. Marks GS, Bnen JF,Nakatsu K,et a1.Carbon monoxide have a physiological function? [J].TrendsPhammcol Sci,1991,12(5):185-188.
21. Panahian N, Yoshiura M, Maines MD. Overexpression of hemeoxygenase-l isneuroproteod vein amodel of permanent middle cerebral artery occlusionin tramgenicmice.[J].Neuroehem,1999,72(3):1187-1203
22.管怀进,龚启荣.现代基础眼科学.北京.1998:92-102.
23.何平,沈馨亚.少突胶质细胞增殖和分化的研究进展.[J].神经解剖学杂志, 2000, 16(2):183.
24. Dawson MR,Polito A,Levine JM.et a1.NG2-expressing glial progenitor cells:an abundant and widespread population of cycling cells in the adult rat CNS.[J].Mel Cell Neurosci,2003,24(2):476-488.
25. McCarthy KD,DeVellis J.Preparation of separate astroglial and oligodendroglia cell cultures from rat cerebraltissue.[J].Cell Biol,1980,85:890.
26.屈卫东,彭晓东,吴德生等.星形胶质细胞、少突胶质细胞分离培养方法研究.[J].卫生研究,1999,9:263.
27. LIU Ping,PENG XI-jia,YE Jian.ela1.The culture and identification of oligodendrocyte of rats optic nerve in vitro Chong Qing Medience , 2003 , 32(3): 330-331
28. Baumann N.Pham-Dinh D.Biology of oligodendrocyte and myelin in the mammalian central nervous system.[J].Physiol Rev,2001,8 1(2):871-927.
29.胡建国,陆佩华,徐晓明.少突胶质细胞生物学功能与相关疾病研究进展.生理科学进展2004,35(1).
30. Chen ZJ,Ughrin Y,Levine JM.Inhibition of axon growth by oligodendrocyte precursor cells.[J].Mol Cell Neurosci,2002,20(1):125-139.
31. Fournier, G.C. Gould, B.P. Liu, S.M. Strittmatter, Truncated soluble Nogo receptor binds Nogo-66 and blocks inhibition of axon growth by myelin , [J] . Neurosci . 22(2002) 8876–8883.
32. Woolf CJ, Bloe ehlinger S.It takes more than two to Nogo.[J].Science,2002,297:1132-1134.
33. Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor . [J] . Science, 2002, 297 :1190-1193.
34. Thom SR,Bhopale VM,Fisher D,el a1.Delayed neuropathology after carbon monoxide poisoning is immune-mediated.[J].Proceedings Nationsl Academy Science USA.2004.101:13660-13665.
35. Wang,Chang Yaoruing,Li Jinsheng.et a1.Expressions of the astrocytes and oligodendrocytes in rat models of delayed neuropathological sequelaeaer CO poisoning and the efect of hyperbaric oxygen treatment on the two kinds of neuroglia cell.[J].China Crit Care Med,2007,27:615-618.
36. Natsumi Hk,Hiroyuki K,Tsutomu A.Age-related changdes of astorocytes , oligodendrocytes and microglia in the mouse hippocampalCA1 sector.Mech Agei Dev.2007.01(005),1-6.
37. LIU Ping,PENG XI-jia,YE Jian,el a1.The culture and identification of oligodendrocyte of rats optic nerve in vitro. Chongqing Medicine , 2003 , 32(3) . 330-331
38. Ahmad AS,Zhuang H,Dore S,et al . Heme oxygenase-l protects brain from acute excitotoxicity[J].Neuroscience,2006,141:1703-1708.
39. Appleton SD,Chretien ML,Mclrughlin BE,et a1.Selective inhibition of heme oxygenase,without inhibition of niric oxide synthase or soluble guanyly cyclase,by metal oporphyrins at low concentrations.[J].Drug Metab Dispo , 1999 , 27 : 1214-1219.
40. Yanagawa T,Omura K,Harada H,et a1.Heme Oxygenase-1 Expression predicts cervical lymph node metastasis of tongue aquamous cell earcino.mas.[J].Oral Oncol,2004,40:21-27.
41. Caballero F,Meiss R,Gimenez A,et a1.Immunohistochemical analy of heine oxygenase-I in preneoplastic and neuroplastic lesions during chemical hepatocarcino genesis.[J] . Exp Pathol,2004,85:213-222
42. Dulak J, Jozkowicz A. Carbon monoxide a“new”gaseous modulator of gene expression.[J].Acta Biochim Pol , 2003 , 50(1) : 31-47. 45 Sehipper HM.Heme oxygenase-l:a role in brain aging and neurodegeneration.Exp Gerontol,2000,35(6-7):821-830
43. Yoshiura M,Maines MD.Overexpression of heme oxygenase—l isneuroproteod vein a model of permanent middle cerebral artery occlusion in tramgenic mice.JNeuroehem,1999, 72(3):1187-1203
44. Bidmon HJ,Emde B,Oermann E,et a1.Heine oxygenase-l(HSP-32)and heme oxygenase-2 induction in neurons and glial cells of cerebral regions and its relation to iron accumulation after focal cortical photothrombosis.Exp Neurol , 2001 , 168(1):1-22
45. Naik JS, WalkerBR.Hemooxygenase-mediated vasodilation involves vascular smoothmuscle cell hyperpolarization.[J].Physiol,2003,285(1):220-228.
46. Panahian N,Yoshiura M,Mainos MD.Overexpressian of heine oxygenase-1 is neuroprotective in a model of permanent middlecerebral artery occlusionin in transgenic mice.[J].Neurochem,1999,72(3):1187-1203.
47. Bidmon HJ,Emde B,Oermann E,et a1.Heine oxygenase-l(HSP-32)and heme oxygenase-2 induction in neurons and glial cells of cerebral regions and its relation to iron accumulation after focal cortical photothrombosis.Exp Neurol , 2001 , 168(1):1-22
48. Reindl M,Khantane S,Ehling R.et a1.Serum and cerebrospinal fluid antibodies to NogoA in patients with multiple sclerosis and acute neurological disorders.[J]. Neuroimmunol,2003,145(2):139.
49. Xijia Peng,Shao zhang Liu,Jian Ye,Rongdi Yuan.Downregulation of Nogo-A Expressionof Oligodendrocytes in Vitro with Antisense Oligodeoxynucleotides . [J].Eyescience,2003.19(3)195-200.
1. Caroni P,Savio T,Schwab.Central nelwous system regeneration: oligodendrocytes and myelin as nonpermissive substrates for neurite growth [J].Prog Brain Res,1988,78:363.
2. Schnell L.Schwab ME.Axonal regeneration in the rat spinal cord produced by an antibody against myelin associated neurite growth inhibitors[J].Nature,1990,343(6255):269.
3. Goldberg JI ,Barres BA.Nogo in nerve regeneration[J].Nature,2000,403(6768):369.
4. Chen MS,Huber A B.Nogo-A is a myelin associated neurite outgrowth inhibitor and an antigen for monoclonal antibodyIN-1[J].Nature,2000,403(6768):434.
5.彭锡嘉,刘少章等原位杂交定位检测神经抑制再生基因Nogo-A mRNA体外培养的视神经少突胶质细胞的表达。重庆医学.2004,33(1):46。
6. Chen M S.Huber AB,Van Der Haar M E,et a1. Nature,2000.403 434-439
7. Josephson A,Trifunovski A,Widmer HR,et al Nogo-receptor gene activity:cellular localization and developmental regulation of mRNA in mice an d humans.[J]Comp Neurol 2002;453(3):292-304
8. Wang XX.Chun SJ,Treloar H.ct at.Localization of Nogo-A and Nogn-66 recepter proteins at sites of axon-myelin and synaptic contact. J Neurosci,2002,22(1 3):5505-55 l 5.
9. Huber AB.Weinmann O,Brosamle C et. a1.Patterns of NogomRNA and protein expression in the developing and adult rat all and after CNS lesions . [J].Neurosri,2002,22 (9):3553-3567.
10. Taketomi M,Kinoshita N,Kimura K et a1.Nogo-A expression in mature oligodendrocytes of rat spinal cord in association with specific molecules.Neurosci Lett,2002;332:37- 40
11. Grandpre T,Nakamura F,Vartanian T et a1.Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein.Nature,2000;403(6768):439-444
12. Chen MS,Huber AB,Schwab ME el a1.Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclona1 antibody IN-1.Nature,2000;403(6768):434-439
13. Woolf CJ,Bloechlinger S.It takes more than two to Nogo.Science。2000:297(5584),1132-1134
14. Fournier AE.GrandPre T,Strittmatter SM .Identification of a receptor m ediatingNogo—66 inhibition of axonal regeneration.[J].Nature,2001,409:341-346.
15. Liu BP,Fournier A,Grandpre T et a1.Myelin associatedgly coprotein as a functional ligand for the Nogo-66 receptor.Science,2002,297(5584):1190-1193
16. Wong ST,Henley JR,Kanning KC et a1.A p75(NTR)and Nogo receptor complex mediates repulsive signals by myelin associated glycoprotein . Nat Neurosci 2002,5,1302- 1328
17. He XL,Bazan JF,McDermott G et a1.Structure of the Nogo receptor ectodomain:a recognition module implicated in myelin inhibition.Neuron,2003;38:177- 185
18. Wang KC,Kim JA,Sivasmkarm R.et a1.P75 interacts with the Nogo receptor as a co-receptor for Nogo,MAG andOMgp.Nature,2002,420(6911):74-78.
19. Skaper SD,Moore SE,Walsh MF.Cell signaling cascades regulating neuronal growth—promoting and inhibitory cues.Prog Neurobiol,2001,65:593- 608
20. Neumann S,Bradke F,Tessier-Lavigne M et a1.Regeneration of sensory axons within the injured spinal cord induced by intraganglionic camp elevation.Neuron,2002,34:885-893
21. Qiu J,Cai D,Dai H et a1.Spinal axon regeneration induced by elevation of cyclic AM P.Neuron,2002,34:895-903
22. Cai D,Deng K,Mellado W et a1.Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro. Neuron,2002;35:711-719
23. Gomez TM,Spitzer NC.In vivo regulation of axon extension and pathfinding by growth cone calcium transients. Nature,1999,397(6717):350-355
24. Zagrebelsky M,Buffo A,Skerra A el a1.Retrograde regulation of growth-associated gene expression in adult rat Purkinje cells by myelin-associated neurite growth inhibitory proteins。JNeurosci,1998;18:7912-7929
25.孟艳,刘梦霞,朱红艳,周江宁,盛树力.Nogo A及其受体在阿尔茨海默病患者脑内的表达。中国临床康复,2003,10(6):102-103。
26. Gil V,Nicolas O,Mingorance A,et a1.NogoA expression in the human hippocampus in normal aging and in Alzheimar disease.[J].Neuropathol Exp Neurol , 2006 , 65(5):433.
27. Park J H,Gimbel DA,GrandPre T,et a1.Alzheimer precursor protein interaction with the Nogo-66 receptor reduces amyloid beta plaque deposition . [J] . Neurosci , 2006,26(5):1386.
28.周建军,冯华,卞修武。Nogo蛋白及其抗体NgR与中枢神经再生。中国临床康复第2004,8(16).3116
29. Oertle T,Marjan E.Nogo-A Inhihits Neurite Outgrowth and Cell Spreading with Three Discrete Regions.[J].Neuroscience.2003,23(13):5393-5406.
30. Fournier AE.GrandPre T,Strittmatter SM .Identification of a receptor m ediating Nogo-66 inhibition of axonal regeneration[J].Nature,2001,409:341-346.
31. Pradat et al.Nogo-A marks motor neuron disease.[J]2007:Ann Neurol,2007,62(1): 1–2.
32. Liao H,Duka T,Teng FY,et a1.C Nogo-66 and myelinassociated glycoprotein (MAG)inhibit the adhesion and migration of Nogo-66 receptor expressing human gliomacells[J].J Neurochem,2004,90(5):115
33. Nishimura AL, Mitne-Neto M, Silva HC, et al. A mutation in the vesicle- trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet,2004;75:822–831.
34. Hadano S, Hand CK, Osuga H, et al. A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat Genet 2001;29:166–173.
2. Mathieu D,Matlueunoif M,Wathlel F.CO poisoning present aspects.[J].Bulletin del academie Nationale Medicine,1996,180(5):965-973.
3.何风生.中华职业医学.[M].北京:人民卫生出版社.1999:424-431.
4. MiroO. Casademont J. barrientos.et al.Mitochondrial cytochrome coxidase inhibiting during acute carbon monoxide poisoning[J].Pharm toxicol.1998.82:199-202
5. Jin WI,Iiu YY,Liu HL,et a1.Intraneuronal location of Nogo-A in the Rat.[J].J Comp Neurol,2003,458:l-10.
6. Liu X,Liu YY,Jin wL,et a1.Nogo-66 receptor at cerebellar cortical glia gap junctions in the rat1[J].Neurosignals,2005,14(3):96.
7. Oertle T,Marjan E.Nogo-A Inhihits Neurite Outgrowth and Cell Spreading with Three Discrete Regions.[J].Neuroscience.2003,23(13):5393-5406.
8. Pozzoli G,MancusoC,Mirtella A,et a1.Carbon monoxide as a novel neuroendocrine modulator inhibition of stimulated corticotropinreleasing hormone release from acute rat hypothalamic explants . [J] . Endocrinology , 1994 , 135(6) : 2314-2317.
9. Chen MS,Huber AB,van der Haar ME.et a1.Nogo-A is a myelin associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1 . [J] . Nature , 2000(6768),403:434-439.
10. Abraham N G,Kappas 18 A.Heme oxygenase and the cardiovascular renal system. [J].Free Radio Biol Med,2005,39(1):1-25.
11. Meyer J.Comparison of carbon monoxide,nitric oxide,and nitrite as inhibitors of the nitrogenase from Clostridiumpasteurianum.Arch Biochem Biophys 1981;210:246-256.
12. Shibahara S,Yoshizawa M ,Suzuki H,Takeda K,Meguro K,EndoK.Functional analysis of eDNA for two types of human heme oxygenase and evidence for their separate regulation.[J].Bioc hem 1993;1 13:214-218.
13. McCoubreyW K,HuangTJ.MainesMD.Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3.Eur J Biochem 1997;247:725-732
14. Wen-Xing YANG,Qi-Lan ZHANG,Hai-Yan HU,.Involvement of endogenous carbon monoxide in regulation of respiratory rhythmin vitro. Acta Physiologica Sinica,June 25.2007,59(3):325-330
15. Mancuse C.Heme oxygenase and it sproduct s in the nervous system.[J].Antioxid Redox Signal,2004,6(5):878-887.
16. Bidmon HJ,Emde B,Oermann E,et a1.Heine oxygenase-l (HSP-32) and hemeoxygenase-2 inductioninn Lronsand glial cells of cerebral regions and its relation to iron accumulation after focal cortical photothrombosis.[J]Exp Neurol,2001,168(1):l-22
17. SehipperHM.Heme oxygenase-l:a role in brain aging and neurodegeneration[J].Exp Gerontol,2000,35(6-7):821-830.
18. Acquaviva R,Campisi A,Raciti G,et a1.Propofol inhibits caspase-3 in astroglial cells:role of heme oxygenase-1.[J].Curr Neurovase Res,2005,2(2):141-148.
19. Volti GL,Sacerdoti D,sangras B,el a1.Carbon monoxide signaling in promoting angiogenesis in human microvessel endothelial cells.[J].Antioxid Redox Signal, 2005,7(56):704-710.
20. Marks GS, Bnen JF,Nakatsu K,et a1.Carbon monoxide have a physiological function? [J].TrendsPhammcol Sci,1991,12(5):185-188.
21. Panahian N, Yoshiura M, Maines MD. Overexpression of hemeoxygenase-l isneuroproteod vein amodel of permanent middle cerebral artery occlusionin tramgenicmice.[J].Neuroehem,1999,72(3):1187-1203
22.管怀进,龚启荣.现代基础眼科学.北京.1998:92-102.
23.何平,沈馨亚.少突胶质细胞增殖和分化的研究进展.[J].神经解剖学杂志, 2000, 16(2):183.
24. Dawson MR,Polito A,Levine JM.et a1.NG2-expressing glial progenitor cells:an abundant and widespread population of cycling cells in the adult rat CNS.[J].Mel Cell Neurosci,2003,24(2):476-488.
25. McCarthy KD,DeVellis J.Preparation of separate astroglial and oligodendroglia cell cultures from rat cerebraltissue.[J].Cell Biol,1980,85:890.
26.屈卫东,彭晓东,吴德生等.星形胶质细胞、少突胶质细胞分离培养方法研究.[J].卫生研究,1999,9:263.
27. LIU Ping,PENG XI-jia,YE Jian.ela1.The culture and identification of oligodendrocyte of rats optic nerve in vitro Chong Qing Medience , 2003 , 32(3): 330-331
28. Baumann N.Pham-Dinh D.Biology of oligodendrocyte and myelin in the mammalian central nervous system.[J].Physiol Rev,2001,8 1(2):871-927.
29.胡建国,陆佩华,徐晓明.少突胶质细胞生物学功能与相关疾病研究进展.生理科学进展2004,35(1).
30. Chen ZJ,Ughrin Y,Levine JM.Inhibition of axon growth by oligodendrocyte precursor cells.[J].Mol Cell Neurosci,2002,20(1):125-139.
31. Fournier, G.C. Gould, B.P. Liu, S.M. Strittmatter, Truncated soluble Nogo receptor binds Nogo-66 and blocks inhibition of axon growth by myelin , [J] . Neurosci . 22(2002) 8876–8883.
32. Woolf CJ, Bloe ehlinger S.It takes more than two to Nogo.[J].Science,2002,297:1132-1134.
33. Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor . [J] . Science, 2002, 297 :1190-1193.
34. Thom SR,Bhopale VM,Fisher D,el a1.Delayed neuropathology after carbon monoxide poisoning is immune-mediated.[J].Proceedings Nationsl Academy Science USA.2004.101:13660-13665.
35. Wang,Chang Yaoruing,Li Jinsheng.et a1.Expressions of the astrocytes and oligodendrocytes in rat models of delayed neuropathological sequelaeaer CO poisoning and the efect of hyperbaric oxygen treatment on the two kinds of neuroglia cell.[J].China Crit Care Med,2007,27:615-618.
36. Natsumi Hk,Hiroyuki K,Tsutomu A.Age-related changdes of astorocytes , oligodendrocytes and microglia in the mouse hippocampalCA1 sector.Mech Agei Dev.2007.01(005),1-6.
37. LIU Ping,PENG XI-jia,YE Jian,el a1.The culture and identification of oligodendrocyte of rats optic nerve in vitro. Chongqing Medicine , 2003 , 32(3) . 330-331
38. Ahmad AS,Zhuang H,Dore S,et al . Heme oxygenase-l protects brain from acute excitotoxicity[J].Neuroscience,2006,141:1703-1708.
39. Appleton SD,Chretien ML,Mclrughlin BE,et a1.Selective inhibition of heme oxygenase,without inhibition of niric oxide synthase or soluble guanyly cyclase,by metal oporphyrins at low concentrations.[J].Drug Metab Dispo , 1999 , 27 : 1214-1219.
40. Yanagawa T,Omura K,Harada H,et a1.Heme Oxygenase-1 Expression predicts cervical lymph node metastasis of tongue aquamous cell earcino.mas.[J].Oral Oncol,2004,40:21-27.
41. Caballero F,Meiss R,Gimenez A,et a1.Immunohistochemical analy of heine oxygenase-I in preneoplastic and neuroplastic lesions during chemical hepatocarcino genesis.[J] . Exp Pathol,2004,85:213-222
42. Dulak J, Jozkowicz A. Carbon monoxide a“new”gaseous modulator of gene expression.[J].Acta Biochim Pol , 2003 , 50(1) : 31-47. 45 Sehipper HM.Heme oxygenase-l:a role in brain aging and neurodegeneration.Exp Gerontol,2000,35(6-7):821-830
43. Yoshiura M,Maines MD.Overexpression of heme oxygenase—l isneuroproteod vein a model of permanent middle cerebral artery occlusion in tramgenic mice.JNeuroehem,1999, 72(3):1187-1203
44. Bidmon HJ,Emde B,Oermann E,et a1.Heine oxygenase-l(HSP-32)and heme oxygenase-2 induction in neurons and glial cells of cerebral regions and its relation to iron accumulation after focal cortical photothrombosis.Exp Neurol , 2001 , 168(1):1-22
45. Naik JS, WalkerBR.Hemooxygenase-mediated vasodilation involves vascular smoothmuscle cell hyperpolarization.[J].Physiol,2003,285(1):220-228.
46. Panahian N,Yoshiura M,Mainos MD.Overexpressian of heine oxygenase-1 is neuroprotective in a model of permanent middlecerebral artery occlusionin in transgenic mice.[J].Neurochem,1999,72(3):1187-1203.
47. Bidmon HJ,Emde B,Oermann E,et a1.Heine oxygenase-l(HSP-32)and heme oxygenase-2 induction in neurons and glial cells of cerebral regions and its relation to iron accumulation after focal cortical photothrombosis.Exp Neurol , 2001 , 168(1):1-22
48. Reindl M,Khantane S,Ehling R.et a1.Serum and cerebrospinal fluid antibodies to NogoA in patients with multiple sclerosis and acute neurological disorders.[J]. Neuroimmunol,2003,145(2):139.
49. Xijia Peng,Shao zhang Liu,Jian Ye,Rongdi Yuan.Downregulation of Nogo-A Expressionof Oligodendrocytes in Vitro with Antisense Oligodeoxynucleotides . [J].Eyescience,2003.19(3)195-200.
1. Caroni P,Savio T,Schwab.Central nelwous system regeneration: oligodendrocytes and myelin as nonpermissive substrates for neurite growth [J].Prog Brain Res,1988,78:363.
2. Schnell L.Schwab ME.Axonal regeneration in the rat spinal cord produced by an antibody against myelin associated neurite growth inhibitors[J].Nature,1990,343(6255):269.
3. Goldberg JI ,Barres BA.Nogo in nerve regeneration[J].Nature,2000,403(6768):369.
4. Chen MS,Huber A B.Nogo-A is a myelin associated neurite outgrowth inhibitor and an antigen for monoclonal antibodyIN-1[J].Nature,2000,403(6768):434.
5.彭锡嘉,刘少章等原位杂交定位检测神经抑制再生基因Nogo-A mRNA体外培养的视神经少突胶质细胞的表达。重庆医学.2004,33(1):46。
6. Chen M S.Huber AB,Van Der Haar M E,et a1. Nature,2000.403 434-439
7. Josephson A,Trifunovski A,Widmer HR,et al Nogo-receptor gene activity:cellular localization and developmental regulation of mRNA in mice an d humans.[J]Comp Neurol 2002;453(3):292-304
8. Wang XX.Chun SJ,Treloar H.ct at.Localization of Nogo-A and Nogn-66 recepter proteins at sites of axon-myelin and synaptic contact. J Neurosci,2002,22(1 3):5505-55 l 5.
9. Huber AB.Weinmann O,Brosamle C et. a1.Patterns of NogomRNA and protein expression in the developing and adult rat all and after CNS lesions . [J].Neurosri,2002,22 (9):3553-3567.
10. Taketomi M,Kinoshita N,Kimura K et a1.Nogo-A expression in mature oligodendrocytes of rat spinal cord in association with specific molecules.Neurosci Lett,2002;332:37- 40
11. Grandpre T,Nakamura F,Vartanian T et a1.Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein.Nature,2000;403(6768):439-444
12. Chen MS,Huber AB,Schwab ME el a1.Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclona1 antibody IN-1.Nature,2000;403(6768):434-439
13. Woolf CJ,Bloechlinger S.It takes more than two to Nogo.Science。2000:297(5584),1132-1134
14. Fournier AE.GrandPre T,Strittmatter SM .Identification of a receptor m ediatingNogo—66 inhibition of axonal regeneration.[J].Nature,2001,409:341-346.
15. Liu BP,Fournier A,Grandpre T et a1.Myelin associatedgly coprotein as a functional ligand for the Nogo-66 receptor.Science,2002,297(5584):1190-1193
16. Wong ST,Henley JR,Kanning KC et a1.A p75(NTR)and Nogo receptor complex mediates repulsive signals by myelin associated glycoprotein . Nat Neurosci 2002,5,1302- 1328
17. He XL,Bazan JF,McDermott G et a1.Structure of the Nogo receptor ectodomain:a recognition module implicated in myelin inhibition.Neuron,2003;38:177- 185
18. Wang KC,Kim JA,Sivasmkarm R.et a1.P75 interacts with the Nogo receptor as a co-receptor for Nogo,MAG andOMgp.Nature,2002,420(6911):74-78.
19. Skaper SD,Moore SE,Walsh MF.Cell signaling cascades regulating neuronal growth—promoting and inhibitory cues.Prog Neurobiol,2001,65:593- 608
20. Neumann S,Bradke F,Tessier-Lavigne M et a1.Regeneration of sensory axons within the injured spinal cord induced by intraganglionic camp elevation.Neuron,2002,34:885-893
21. Qiu J,Cai D,Dai H et a1.Spinal axon regeneration induced by elevation of cyclic AM P.Neuron,2002,34:895-903
22. Cai D,Deng K,Mellado W et a1.Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro. Neuron,2002;35:711-719
23. Gomez TM,Spitzer NC.In vivo regulation of axon extension and pathfinding by growth cone calcium transients. Nature,1999,397(6717):350-355
24. Zagrebelsky M,Buffo A,Skerra A el a1.Retrograde regulation of growth-associated gene expression in adult rat Purkinje cells by myelin-associated neurite growth inhibitory proteins。JNeurosci,1998;18:7912-7929
25.孟艳,刘梦霞,朱红艳,周江宁,盛树力.Nogo A及其受体在阿尔茨海默病患者脑内的表达。中国临床康复,2003,10(6):102-103。
26. Gil V,Nicolas O,Mingorance A,et a1.NogoA expression in the human hippocampus in normal aging and in Alzheimar disease.[J].Neuropathol Exp Neurol , 2006 , 65(5):433.
27. Park J H,Gimbel DA,GrandPre T,et a1.Alzheimer precursor protein interaction with the Nogo-66 receptor reduces amyloid beta plaque deposition . [J] . Neurosci , 2006,26(5):1386.
28.周建军,冯华,卞修武。Nogo蛋白及其抗体NgR与中枢神经再生。中国临床康复第2004,8(16).3116
29. Oertle T,Marjan E.Nogo-A Inhihits Neurite Outgrowth and Cell Spreading with Three Discrete Regions.[J].Neuroscience.2003,23(13):5393-5406.
30. Fournier AE.GrandPre T,Strittmatter SM .Identification of a receptor m ediating Nogo-66 inhibition of axonal regeneration[J].Nature,2001,409:341-346.
31. Pradat et al.Nogo-A marks motor neuron disease.[J]2007:Ann Neurol,2007,62(1): 1–2.
32. Liao H,Duka T,Teng FY,et a1.C Nogo-66 and myelinassociated glycoprotein (MAG)inhibit the adhesion and migration of Nogo-66 receptor expressing human gliomacells[J].J Neurochem,2004,90(5):115
33. Nishimura AL, Mitne-Neto M, Silva HC, et al. A mutation in the vesicle- trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet,2004;75:822–831.
34. Hadano S, Hand CK, Osuga H, et al. A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat Genet 2001;29:166–173.