用户名: 密码: 验证码:
甘肃鼢鼠(Myospalax cansus)视觉系统细胞凋亡研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
视觉系统在动物通讯中占据主导地位,有关其适应进化一直是人们关注的焦点。营严格地下洞道生活的啮齿动物,由于适应地下黑暗的生活环境,其视觉系统的形态结构、功能等在进化中表现出高度的趋同现象,如视器变小,视觉退化乃至消失等。这些特征为研究地下啮齿动物视觉系统的适应进化提供了十分理想的实验材料,也将对地下啮齿动物视觉系统适应进化机制的研究起积极促进作用。本研究以甘肃鼢鼠(Myospalax cansus)为材料,运用吉姆萨—瑞氏染色法观察不同日龄甘肃鼢鼠视网膜细胞的凋亡形态和数量、免疫组织化学法对各视觉核团中Bax、Bcl-2表达量进行测定,探讨甘肃鼢鼠视觉系统细胞凋亡情况。结果如下:
     1.从0日龄开始甘肃鼢鼠视网膜内出现凋亡细胞,凋亡指数为:26.9±0.441%,这说明甘肃鼢鼠出生后其视网膜就伴随着细胞凋亡。
     2.大多数凋亡细胞出现在视网膜视杆视锥层向内的各层,特别是外核层、内核层和神经节细胞层,这说明视杆视锥层及其向内的各层细胞才是视觉通路中的主要神经元。
     3.0日龄、7日龄、14日龄甘肃鼢鼠视网膜细胞凋亡指数逐渐增大,14日龄细胞凋亡指数最大,而后细胞凋亡指数减小,并维持在相对稳定水平,说明甘肃鼢鼠视网膜细胞主要在出生后两周的时间内发生凋亡,14日龄时为凋亡峰,而后凋亡又减少。
     4.0日龄、7日龄、14日龄甘肃鼢鼠视觉核团Bax和Bcl-2的比率呈增加趋势,14日龄时Bax和Bcl-2的比率最大。这说明甘肃鼢鼠出生后两周,视觉核团细胞凋亡程度逐渐增大,14日龄时细胞凋亡程度最大。
     5.14日龄往后甘肃鼢鼠视觉核团Bax和Bcl-2的比率维持在相对稳定的水平,这说明当机体的内环境达到稳定后,细胞凋亡也随之维持在一个相对稳定的水平。另外,这一结果可能还与睁眼有关。
     6.每一年龄段甘肃鼢鼠外侧膝状体背侧核、外侧膝状体腹侧核Bax蛋白表达量较其它核团多。这说明在整个视觉信息的传递过程中,外侧膝状体起着极其重要的作用。
     总之,本研究表明甘肃鼢鼠视觉系统的细胞凋亡主要发生在出生后两周内;14日龄时细胞凋亡程度最大,为凋亡峰;而后细胞凋亡保持在一个相对稳定的水平。
Visual system in animal's communications occupys a dominant position,and its evolutionary adaptation has been the focus of attention.Owning to adapting to subterranean dark ecotope, morphologic structures and functions of visual system in subterranean rodents show high convergence,such as small visual organs,regressive visual ability and even no such ability,which provides ideal materials for the studies on visual system evolution of these animals.And it will assist in revealing the adaptive evolutionary mechanism of visual system of subterranean rodents.Using Giemsa-Wright staining to observe the form and the number of apoptotic cells of retinal and immunohistochemical method to measure the number of Bax and Bcl-2 of every visual nucleus in different day old groups of Myospalax cansus,and to explore the apoptosis of visual system.The results are as follows:
     1.From 0th day old apoptotic cells appeared in the retinal of Myospalax cansus.The apoptosis index is 26.9±0.441%.This indicates that after birth the retinal of Myospalax cansus associated with apoptosis.
     2.Most of apoptotic cells in the retina appeared inside photoreceptor outer segment, especially outer nuclear layer,inner nuclear layer and ganglion cell layer.This indicates that cells which inside photoreceptor outer segment are the major neurons of visual pathway.
     3.The apoptosis index of retinal cells gradually increased along with the dates growth of 0th, 7th and 14th day old.The apoptosis index of 14th day old was the maximum,then decreased,and stabled a relative level.This shows that the apoptosis of retinal cells mainly occur within two weeks after birth and apoptotic peak appears at 14th day old,then apoptosis reduced.
     4.The ratio of Bax and Bcl-2 gradually increased along with the dates growth of 0th,7th and 14th day old.,and the ratio of Bax and Bcl-2 was the largest.This shows that the degree of apoptosis gradually increased and the degree of apoptosis is the greatest in 14th day old.
     5.The ratios of Bax and Bcl-2 stabled a relative level.This shows that apoptosis also stable a relative level when internal environment of organism reaches stable.In addition,this result may be related with eye opening.
     6.The number of Bax expression of the dorsal lateral geniculate nucleus and the ventral lateral geniculate nucleus in each age section of Myospalax cansus were more than the one of other visual nucleus.This indicates that in the entire transmission process of visual information,the lateral geniculate nucleus plays a extremely important role.
     In brief,this research indicates that apoptosis of the vision system of Myospalax cansus mainly occurres within two weeks after birth.The degree of apoptosis is the greatest in 14th day old and apoptotic peak appears at 14th day old.Then apoptosis stable a relative level.
引文
[1]Ellerman J.R.,1956.The subterranean mammals of the world.[J]Trans R,Soc S Afr.,35:11-20.
    [2]Nevo E.,1979.Adaptive convergence and divergence of subterranean mammals.[J]Annu.Rev.Ecol.Syst.,10:269-308.
    [3]Huntly N.,Lnouye R.S.,1988.Pocket gophers in ecosystem:patterns and mechanisms[J]Bioscience,38:786-793.
    [4]Mielke H.W.,1977.Mound building by pocket gophers(Geomyidae):their impact on soil and vegetation in North America.[J]Biogeogr,4:171-180.
    [5]Andersen D.C.,1987.Below-ground herbivory in natural communities:a review emphasizing fossorial animals.[J]Q Rev Biol.,62:261-286.
    [6]Pavel Nemec,Hynek Burda,Leo Peichl,2004.Subcortical visual system of the African mole-rat Cryptomys anselli:to see or not to see?[J]European Journal of Neuroscience.,20:757-768.
    [7]Nevo E.,1999.Mosaic Evolution of Subterranean Mammals:Regression.Progression,and Global Convergence.[M]Oxford University Press,Oxford.
    [8]Burda H.,Bruns V.,Muller M.,1990.Sensory adaptations in subterranean mammals,In Nevo,E.& Reig,O.A.(eds),Evolution of Subterranean Mammals at the Organismal and Moleculars Levels.Alan R.Liss,Inc..New York:269-294.
    [9]Kimchi T.,Terkel J.,2002.Seeing or not seeing.[J]Neurobiol.,12:728-734.
    [10]De Jong W.W.,Hendriks W.,Sanyal S.,Nevo E.,1990.The eye of the blind mole rat(Spalax ehrenbergi):Regressive evolution at the molecular levels.[A]In:Nevo E & Reig O A eds.Evolution of subterranean mammals at the organismal and molecular levels.[C]New York:Wiley-Liss,383-395.
    [11]Macdonald D.,1984.The encyclopedia of mammals.[M]New York:Facts on File Publications.
    [12]Eloff G.,1951.Adaptation in rodent moles and insectivorous moles.and the theory of convergence.[J]Nature,168:1001-1002.
    [13]Poduschka W.,1978.Zur Frage der Wahrnehmung von Lichtreizen durch die Mullratte,Cryptomys hottentotus.[J]Saugetierkundliche Mitteilungen 26:269-274.
    [14]Jarcis J.U.M.,1973.Activity patterns in the mole-rats Tachyoryctes splendens and Heliophobius argenteocinereus.[J]Zoologica Africana,8:101-119.
    [15]Ognev S.I.,1950.Mammals of the U.S.S.R.and adjacent countries.[M]Washington D.C.:Smithsonian Institution and NSF.
    [16]成令忠等.1993.组织学[M].人民卫生出版社,641-688.
    [17]Cei G.,1946.Locchio di heterocephalus glaber r(u|¨)ppell.Note anatomo-descrittive istologiche.[J]Monit Zool Ital,55:89-96.
    [18]Eloff G..,1958.The functional and structural degeneration of the eye of the South African rodent moles,Cryptomys bigalkei and Bathyergus maritimus.[J]S Afr J Sci.,54:293-302.
    [19]Sanyal S.,Jansen H.G..,De Grip W.J.,Nevo E.,De Jong W.W..,1990.The eye of the blind mole rat,Spalax ehrenbergi.Rudiment with hidden function.[J]Invest Ophthalmol Vis Sci,31:1398-1404.
    [20]张育辉,刘加坤.1994.七种啮齿动物视觉器官形态结构的比较研究.[J]兽类学报.14(3):189-194.
    [21]Cernuda-Cernuda R.,De Grip W.J.,Cooper H.M.,Nevo E.,Garcia-Fernandez J.M.,2002.The retina of Spalax ehrenbergi:novel histologic features supportive of a modified photosensory role.[J]Investigative Ophthalmology & visual science,43:2374-2383.
    [22]Peichl Leo.Nemec Pavel.Burda Hynek.,2004.Unusual cone and rod properties in subterranean African mole-rats(Rodentia,Bathyergidae).[J]European Journal of Neuroscience,19(6):1545-1558.
    [23]Herbin M.,Rio J.P.,Reperant J.,Cooper H.M.,Lemire M.,1993.Ultrastructural analysis of the optic nerve in microphthalmic rodents(Spalax leucodon).[J]C R.Acad Sci Serie,316:251-258.
    [24]Herbin M.,Rio J.R,Reperant J.,Cooper H.M.,Nero E.,Lemire M.,1995.Ultrastructural study of the optic nerve in blind mole-rats(Spalacidae,Spalax).[J]Vis.Neurosci,12:253-261.
    [25]Omlin F.X.,1997.Optic disc and optic nerve of the blind Cape mole-rat (Georychus capensis):A proposed model for naturally occurring reactive gliosis.[J]Brain Research Bulletin,44(5):627-632.
    [26]Guillery R.W.,1970.Colonnier.M.:Z.Zellforsch.,103:90-108.
    [27]LeVay S.,Ferster P.,1977.Relay cell classes in the lateral geniculate nucleus of the cat and the effect of visual dep rivation.[J]Comp Neurol,172:563-584.
    [28]Guillery R.W.,1972.Binocular competition in the control of geniculate cell growth.[J].Comp Neurol,144:117-129.
    [29]Moore R.Y.,Weis R.,Moga M.,2000.Efferent projections of the intergeniculate leaflet and the ventral lateral geniculate nucleus in the rat.[J]Comp Neurol,420:398-418.
    [30]Ahmed A.K.M.,Dong K.,Yamadori T.,1995.A retrograde double-labelling study of retinal ganglion cells that project to silaterally to VLGN and LPN rather than DLGN and SC,in albinorat.[J]Brain Res.,674:275-282.
    [31]Yucel Y.H.,Zhang Q.,Gup ta N.,2000.Loss of neurons in magnocellular and parvocelluar layers of the lateral geniculate nucleus in glaucoma.[J]Arch Ophthalmol.,118:378-384.
    [32]Wang X.,Tay S.S.W.,Ng Y.K.,2000.Nitric oxide,microglial activities and neuronal cell death in the lateral geniculate nucleus of glaucomatous rats.[J]Brain Res,878:136-137.
    [33]曾明兵.王宁利,吴河坪,2002.大鼠视神经钳伤后外侧膝状体细胞损伤的研究.[J]中华眼科杂志,38:308-310.
    [34]卢艳,张晶瑶.1999.糖尿病对中枢神经系统的影响.[J]国外医学眼科学分册,3:306-309.
    [35]Trejo L.J.,Cicerone C.M.,1984.Cells in the pretectal olivary nucleus are in the pathway for the direct light reflex of the pupil in the rat.[J]Brain Res.,300:49-62.
    [36]Leichnitz G.R.,1990.Preoccipital cortex receives a differential input from the frontal eye field and projects to the pretectal olivary nucleus and other visuomotor related structures in the rhesus monkey.[J]Vis.Neurosci,5:123-133.
    [37]Thompson R.,Rich I.,1961.A discrete diencephalic pretectal area critical for retention of visual habits in the rat.[J]Exp Neurol,4:436-443.
    [38]Urbaitis J.C.,Meikle T.H.,1968.Relearning a dark-light discrimination by cats after cortical and collicular lesions.[J]Exp.Neurol,20:295-311.
    [39]Clarke R.J.,Ikeda H.,1985.Luminance and darkness detectors in the olivary and posterior pretectal nuclei and their relationship to the pupillary light reflex in the rat.[J]Exp.Brain Res.,57:224-232.
    [40]Lund R.D.,Lund J.S.,1965.The visual system of the mole.Talpa europaea.[J] Exp.Neurol,13:303-316.
    [41]Bronchti G.,Rado R.,Terkel J.,Wollberg Z.,1991.Retinal projections in the blind mole rat:A WGA-HPR tracing study of a natural degeneration.[J]Dev Brain Res.,8:159-170.
    [42]Cooper H.M.,Herbin M.,Nevo E.,1993.Visual system of a naturally microphthalmic mammal:the blind mole rat,Spalax ehrenbergi.[J]Comp Neurol,328:313-350.
    [43]Cooper H.M.,Herbin M.,Nevo E.,1993b.Ocular regression conceals adaptive progression of the visual system in a blind subterranean mammal.[J]Nature,361:156-159.
    [44]Oelschl(a|¨)ger H.H.A.,Nakamura M.,Herzog M.,Burda H.,2000.Visual system labeled by c-Fos immunohistochemistry after light exposure in the 'blind'subterranean Zambian mole-rat(Cryptomys anselli).[J]Brain Behav.Evo.,55:209-220.
    [45]Schneider G E.,1969.Two visual system.[J]Science,163:895-902.
    [46]付煜西,高宏峰,S.A.George,王书荣,1997.γ-氨基丁酸及其受体在家鸽基底视束核中的作用.[J]中国科学(C辑),27(3):211-215.
    [47]Tyler C.J.,Fire K.V.,Devries G.J.,1995.Distribution of GAD-like immunoreactivity in the retina and central visual system of rana pipiens.[J]J Comp Neurol,353:439-450.
    [48]Britto L.R.G.,Hamassaki D.E.,Keyser K.T.,et al.,1989.Neurotransmitters,receptors,and neuropeptides in the accessory optic system:an immunohistochemical survey in the pigeon(Columba livia).[J]Visual Neuroscience,3:463-475.
    [49]Granda R.H.,Crossland W.J.,1989.GABA-like immunoreactivity of neurons in the chicken diencephalon and mesencephalon.[J]J Comp Neurol,287:455-469.
    [50]Schmidt M.,Lewald J.,Vandertogt C.,et al.,1994.The contribution of GABA-mediated inhibition to response properties of neurons in the nucleus of the optic tract in the rat.[J]European J Neurosci,6(11):1656-1661.
    [51]Cadasseau J.,Roger M.,1985.Afferent projections to superior colliculus in the rat with special attention to the deep layers.[J]J Hirnforsh,26(6):667-681.
    [52]Zhu J.J.,Lo F.S.,1997.Recurrent inhibitory interneurons of the rabbitps lateral posterior pulvinar complex.[J]Neurophysiol,78(6):3117-3124.
    [53]Kerr JFR,et al.,1972.Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics.[J]Br J Cancer.26:239-257
    [54]童善庆.陆德源.1995.细胞凋亡及其意义.[J]国外医学内科分册,22(7):293-296.
    [55]赵卫红,寿好长,闫福岭.1997.细胞凋亡[M].河南:河南医科大学出版社,7-12.
    [56]Whyllie AH,1980.Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activity.[J]Nature.284:555-556.
    [57]成军,斯崇文,1995.细胞凋亡的研究进展.[J]国外医学(流行病学传染病学分册),22(3):101-104.
    [58]Williams GT.et al.,1993.Molecular regulation of apoptosis:genetic controls on cell death.[J]Cell.74:777-779.
    [59]Nakai M,el al.,1993.Biochemical and Biophysical Research Communications[M]196:233-239.
    [60]Quirk SM,Cowan RG,Joshi SG,el al.,1995.Fas antigen-mediated apoptosis in human granulose/luteal cells.[J]Biol Reprod.52(2):279-287.
    [61]Trauth BC.Peters AM.1989.Monoclonal antibody-mediated tumor regression by induction of apoptosis.[J]Science.245:301-304.
    [62]吴永青.葛坚,1996.细胞凋亡与眼病.[J]国外医学眼科学分册,20(5):257-265.
    [63]Tsujimoto Y.Adachi M.Cossman J.et al.,1985.Variant translocation of the bcl-2gene to immunoglobulin lambda light chain gene in chronic lymphocytic leukemia.[J]Proc Natl Acad Sci USA.86(8):2771-2774.
    [64]Kowaltowski A J,Fenton RG,Fiskum G,2004.Bcl-2 family proteins regulate mitochon drial reactive oxygen production and protect against oxidative stress.[J]Free Radic Bio Med,37(11):1845-1853.
    [65]Merry DE,Veis DJ.Hickey WF,et al.,1994.Bcl-2 protein expression is widespread in the developing neurons system and retained in the adult PNS.[J]Derelopment,120(2):301-307.
    [66]Oltvai ZN,Milliman CL,Korsmeyer SJ,1993.Bcl-2 heterodimerizes in vivo with a conserved homolog,bax.that accelerates programmed cell death.[J]Cell,74(4):609-619.
    [67]Macaya A.,1996.Apoptosis in the nervous system.[J]Rev Neurol,24(135):1356-1360.
    [68]Yin X.M.,Oltvai Z.N.,Korsmeyer S.J.,1994.BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax.[J]Nature,369(6478):321-333.
    [69]Yang J,Wu LJ,Tashino S,Onodera S,Ikejima T.,2008.Reactive oxygen species and nitric oxide regulate mitochondria-dependent apoptosis and autophagy in evodiamine -treated human cervix carcinoma HeLa cells.[J]Free radio Res.,42(5):492-504.
    [70]White E,1994.p53 guardian of RB.[J]Nature.371:21-22.
    [71]White E,Livanos E M,Tlsy TD,1994.Differential disruption of genomic integrity and cell cycle regulation in normal human fibroblasts by the HPV oncoproteins.[J]Genes and Development,8:666-677.
    [72]Quiqley HA,Nickells RW,Kerriqan LA,et al.,1995.Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis.[J]Invest Ophthalmol Vis Sic.,36(5):774-786.
    [73]Cook B,Lewis GP,Fisher SK,et al.,1995.Apoptotic photoreceptor degeneration in experimental retinal detachment.[J]Invest Ophthalmol Vis Sic.,36:990-996.
    [74]Nucci C.,Piccirilli S.,Bagetta G.,1997.N-methyl-D-aspartate(NMDA)and non-NMDA glutamate receptor antagonists protect from apoptosis induced in the lateral geniculate nucleus of rabbits exposed to the dark.[J]Neurosci.,229:185-188.
    [75]Ramoa A.S.,Prusky G.,1997.Retinal activity regulates developmental switches in functional properties and ifenprodil sensitivity of NMDA receptors in the lateral geniculate nucleus.[J]Brain Res Dev Brain Res,101:165-175.
    [76]曹志东,王梅春,1994.甘肃鼢鼠的生物学特性研究.[J]甘肃农业科技.5:32-33.
    [77]Nevo E.,1995.Mammalian evolution underground.The ecological-genetic-phenetic interfaces.[J]Acta Theriol.,3:9-31.
    [78]Rado R.,Bronchti G.,Wollberg Z.,Terkel J.,1992.Sensitivity to light of the blind mole rat:Behavioral and neuroanatomical study.[J]Israel Journal of Zoology,38(3-4):323-331.
    [79]Goldman B.D.,Goldman S.L.,1997.Circadian patterns of locomotor activity and body temperature in blind mole rats,Spalax ehrenhergi.[J]Biol.Rhythms,12:348-361.
    [80]Vuillez P.,Herbin M.,Cooper,H.M.,1994.Photic induction of Fos immunoreactivity in the suprachiasmatic nuclei of the blind mole rat(Spalax ehrenbergi).[J]Brain Res.,654:81-84.
    [81]Avivi A.,Oster H.,2002.Circadian genes in a blind subterranean mammal Ⅱ:Conservation and uniqueness of the three Period homologs in the blind subterranean mole rat,Spalax ehrenbergi superspecies.[J]Proc.Natl.Acad.Sci.,99(18):11718-11723.
    [82]Hough R.B.,Avivi A.,Davis J.,2002.Adaptive evolution of small heat shoch protein alpha B-crystallin promoter activity of the blind subterranean mole rat,Spalax ehrenbergi.[J]Natl.Acad.Sci.99(12):8145-8150.
    [83]DAI yue-Qin,LI Jin-Gang,HE Jian-Ping et al.,2006.Postnatal development of the retina in root vole Microtus oeconomus.[J]Acta Zoologica Sinica.,52(2):376-382.
    [84]刘敏,李金钢,王廷正.1995.延安林区甘肃鼢鼠种群年龄结构的研究.[J]黄土高原林区鼢鼠综合管理研究.33-41.
    [85]蔡浩然,马万禄,1978.视觉的分子生理学基础[M].科学出版社.5-6.
    [86]Glickstein M.,Brown-Grant K.,Raisman,1972.[J]Journal of anatomy,111(3):515.
    [87]牛建军,王一,曾玉晓等,2007.重组人促红细胞生成素对视神经不完全损伤后视网膜神经元的保护作用.[J]眼科新进展.27(7):501-504.
    [88]Dong W,Muramoto W,Nagai Y,et al.,2006.Retinal neuronal cell is a toxicological target of tributyltin in developing zebrafish.[J]J Vet Med Sci.,68(6):573-579.
    [89]Rodger J,King CE,Lukehurst S,et al.,2006.Changing Pax6 expression correlates with axon outgrowth and restoration of topography during optic nerve regeneration.Neuroscience.,142(4):1043-1054.
    [90]Lund R D.,Lund J S.,1965.The visual system of the mole,Talpa europaea.[J]Exp.Neurol,13:303-316.
    [91]章海军,2004.视觉及其应用技术[M].浙江大学出版社,41-42.
    [92]Hubel D.H.,Wiesel T.N.,1963.Receptive Fields of Cells in Striate Cortex of Very Young.Visually Inexperienced Kittens.[J]Neurophysiol.,26:994-1002.
    [93]Wiesel T.N.,Hubel D.H.,1963.Single-Cell Responses in Striate Cortex of Kittens Deprived of Vision in One Eye.[J]Neurophysiol.,26:1003-1017.
    [94]Blakemore C.,Cooper G.F.,1970.Development of the Brain depends on the Visual Environment.[J]Nature,228:477-478.
    [95]Blakemore C.,Van Sluyters R.C.,1974.Reversal of the Physiological Effects of Monocular Deprivation in Kittens:Further Evidence for a Sensitive Period.[J]Physiol.,237:195-216.
    [96]Behl C.,Hovey L.,Krajewski S.,1993.Bcl-2 prevents killing of neuronal cells by glutamate but not by amyloid beta protein.[J]BiochemBiophysRes.Commun,197(2):949-956.
    [97]Steinman H.M.,1995.The bcl-2 oncoprotein function as pro-oxidant.[J]Biol.Chem.,270(8):3487-3490.
    [98]Gilbert M.S.,Saad A.H.,Rupnow B.A.,1996.Association of bcl-2 with membrane hyperpolarization and radioresistance.[J]Cell Physiol,168(2):114-122.
    [99]Krajewski S.,Tanaka S.,Takayama S.,1993.Investigation of subcellular distribution of bcl-2 oncoprotein resitlence in the nuclear envelope,endoplasmic reticulum,and outer mitochondrial membranes.[J]Cancer Res.,53(19):4701-4714.
    [100]Stefan I,Claudia W,Stanislao K,et al.1997.Up-regulation of Bax protein in degenerating retinal ganglion cells precedes apoptotic cell death after optic nerve lesion in the rat.[J]Eur J Neurisci,9(8):1763-1772.
    [101]Porciatti V,Pizzorusso T,Chierzi S,el al.,1998.Protection of retinal ganglion cells and preservation of function after optic nerve lesion in Bcl-2 transgenic mice.[J]Vison Res,38(10):1517-1543.
    [102]寿天德主编,2001.神经生物学[M].高等教育出版社,173.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700