HCMV感染人海马NSCs分化Astrocytes并诱导细胞凋亡的研究
摘要
目的研究人类巨细胞病毒(HCMV)能否感染体外培养的由人海马神经干细胞(NSCs)分化成的星形胶质细胞(Astrocytes),并观察病毒感染对细胞凋亡的影响,为探讨先天性巨细胞病毒感染致脑发育异常的机制提供理论依据。
方法体外分离、培养人海马NSCs,添加血清诱导其定向分化为星形胶质细胞,倒置显微镜下观察细胞的形态学特点并利用间接免疫荧光染色方法通过检测其各自的标志蛋白进行鉴定。然后用HCMV AD169株感染人星形胶质细胞(MOI=1),镜下观察感染后细胞的形态学变化,利用间接免疫荧光技术检测细胞内病毒基因产物-IE蛋白的表达,采用流式细胞术PI染色和细胞涂片Annexin V-FITC/PI染色法检测感染细胞的凋亡情况。同时收集感染细胞的培养液,接种到正常人胚肺二倍体细胞(MRC-5)中,观察有无典型的HCMV致细胞病变出现。
结果体外原代培养的人海马NSCs以神经球的形式悬浮生长,绝大多数细胞都表达NSCs的标记物-巢蛋白(nestin),诱导其分化后,细胞高表达星形胶质细胞的标志物—神经胶质纤维酸性蛋白(GFAP)。HCMV AD169感染星形胶质细胞7天后,细胞出现肿胀、变大、变圆等典型病变,胞核内检测到HCMV即刻早期基因的表达产物-IE蛋白。流式细胞术PI单染结果显示:MOI=1时,感染组细胞凋亡比例为14.72%±5.78%,明显高于正常对照组7.59%±2.33%,两组比较有统计学意义(t=3.18,P<0.05)。细胞涂片Annexin V-FITC/PI染色结果也显示,感染组细胞凋亡比例高于对照组。收集感染细胞的培养液并接种到HCMV的完全容许性细胞—MRC-5中,一周后细胞也出现上述典型病变,证明HCMV可在星形胶质细胞内增殖、复制并释放到胞外。
结论(1)在体外培养的由人NSCs分化成的星形胶质细胞中,HCMV AD169能够建立增殖性感染,该细胞是HCMV的容许性细胞。
(2)HCMV感染诱导体外培养的由人NSCs分化成的星形胶质细胞凋亡,这可能与先天性巨细胞病毒感染导致脑发育异常有关。
Objective To study the susceptibility of astrocytes that differentiated from human embryonic hippocampus neural stem cells(NSCs) to HCMV AD169 infection and the effect of HCMV infection on apoptosis of astrocytes in vitro.
Methods Human embryonic hippocampus NSCs were isolated and cultured in vitro and identified by detecting the expression of Nestin protein with indirect immunofluorescence method,then cells were induced to differentiate into astrocytes.Astrocytes cultured in vitro were identified by observing their morphologic characteristics under inverted microscope and detecting the glial fibrillary acidic protein(GFAP) by indirect immunofluorescence. Then astrocytes were infected with HCMV strain AD169 at 1 multiplicity of infection(MOI=1),Viral-associated cytopathic effects were observed under inverted microscope,and indirect immunofluorescence was used to examine the expression of HCMV immediate early gene product—IE proteins,PI staining by Flow cytometry and slide staining with Annexin V-FITC/PI were both used to detect the apoptosis of astrocytes. The medium from infected cells was collected to infect fibroblasts(MRC-5),which are fully permissive for HCMV infection.
Results Most of NSCs cultured in vitro expressed protein—Nestin,which is the recognized NSCs marker,then were induced to differentiate,7 days later,cells strongly expressed GFAP—markers of astrocytes.7 days after HCMV infected astrocytes, cytopathic effects(Swelling,bigger and so on) were observed and HCMV gene product-IE protein were detected in most cells.The results of flow cytometry assay showed that the proportion of apoptotic cells in the infection group(14.72%±5.78%) was higher than that in the normal group(7.59%±2.33%),and there was statistical significance between the two groups(t=3.18,P<0.05).At the same time,staining on the slide also showed the same results:much more cells in the infection group than that in the normal group were positive of apoptotic stain.Fibroblasts exposed the medium from infected cells were also observed typically Virus-induced cytopathic.
Conclusion
(1) HCMV can infect human astrocytes that differentiated from human embryonic hippocampus NSCs in vitro;
(2) HCMV infection can induce astrocytes apoptosis in vitro.This effect may provide part of the explanation for the abnormalities in brain development associated with congenital HCMV infection.
方法体外分离、培养人海马NSCs,添加血清诱导其定向分化为星形胶质细胞,倒置显微镜下观察细胞的形态学特点并利用间接免疫荧光染色方法通过检测其各自的标志蛋白进行鉴定。然后用HCMV AD169株感染人星形胶质细胞(MOI=1),镜下观察感染后细胞的形态学变化,利用间接免疫荧光技术检测细胞内病毒基因产物-IE蛋白的表达,采用流式细胞术PI染色和细胞涂片Annexin V-FITC/PI染色法检测感染细胞的凋亡情况。同时收集感染细胞的培养液,接种到正常人胚肺二倍体细胞(MRC-5)中,观察有无典型的HCMV致细胞病变出现。
结果体外原代培养的人海马NSCs以神经球的形式悬浮生长,绝大多数细胞都表达NSCs的标记物-巢蛋白(nestin),诱导其分化后,细胞高表达星形胶质细胞的标志物—神经胶质纤维酸性蛋白(GFAP)。HCMV AD169感染星形胶质细胞7天后,细胞出现肿胀、变大、变圆等典型病变,胞核内检测到HCMV即刻早期基因的表达产物-IE蛋白。流式细胞术PI单染结果显示:MOI=1时,感染组细胞凋亡比例为14.72%±5.78%,明显高于正常对照组7.59%±2.33%,两组比较有统计学意义(t=3.18,P<0.05)。细胞涂片Annexin V-FITC/PI染色结果也显示,感染组细胞凋亡比例高于对照组。收集感染细胞的培养液并接种到HCMV的完全容许性细胞—MRC-5中,一周后细胞也出现上述典型病变,证明HCMV可在星形胶质细胞内增殖、复制并释放到胞外。
结论(1)在体外培养的由人NSCs分化成的星形胶质细胞中,HCMV AD169能够建立增殖性感染,该细胞是HCMV的容许性细胞。
(2)HCMV感染诱导体外培养的由人NSCs分化成的星形胶质细胞凋亡,这可能与先天性巨细胞病毒感染导致脑发育异常有关。
Objective To study the susceptibility of astrocytes that differentiated from human embryonic hippocampus neural stem cells(NSCs) to HCMV AD169 infection and the effect of HCMV infection on apoptosis of astrocytes in vitro.
Methods Human embryonic hippocampus NSCs were isolated and cultured in vitro and identified by detecting the expression of Nestin protein with indirect immunofluorescence method,then cells were induced to differentiate into astrocytes.Astrocytes cultured in vitro were identified by observing their morphologic characteristics under inverted microscope and detecting the glial fibrillary acidic protein(GFAP) by indirect immunofluorescence. Then astrocytes were infected with HCMV strain AD169 at 1 multiplicity of infection(MOI=1),Viral-associated cytopathic effects were observed under inverted microscope,and indirect immunofluorescence was used to examine the expression of HCMV immediate early gene product—IE proteins,PI staining by Flow cytometry and slide staining with Annexin V-FITC/PI were both used to detect the apoptosis of astrocytes. The medium from infected cells was collected to infect fibroblasts(MRC-5),which are fully permissive for HCMV infection.
Results Most of NSCs cultured in vitro expressed protein—Nestin,which is the recognized NSCs marker,then were induced to differentiate,7 days later,cells strongly expressed GFAP—markers of astrocytes.7 days after HCMV infected astrocytes, cytopathic effects(Swelling,bigger and so on) were observed and HCMV gene product-IE protein were detected in most cells.The results of flow cytometry assay showed that the proportion of apoptotic cells in the infection group(14.72%±5.78%) was higher than that in the normal group(7.59%±2.33%),and there was statistical significance between the two groups(t=3.18,P<0.05).At the same time,staining on the slide also showed the same results:much more cells in the infection group than that in the normal group were positive of apoptotic stain.Fibroblasts exposed the medium from infected cells were also observed typically Virus-induced cytopathic.
Conclusion
(1) HCMV can infect human astrocytes that differentiated from human embryonic hippocampus NSCs in vitro;
(2) HCMV infection can induce astrocytes apoptosis in vitro.This effect may provide part of the explanation for the abnormalities in brain development associated with congenital HCMV infection.
引文
1、 Peckham CS.Cytomegalovirus infection:congenital and neonatal disease.Scand J Infect Dis Suppl,1991,80:82-87.
2、闻玉梅,陆德源,何丽芳等.现代医学微生物学.上海:上海医科大学出版社,1991,925-948.
3、金锐.巨细胞病毒特性综述.科协论坛,2007,7(下):38.
4、王政禄,印志琪,李卉等.HCMV(pp65)抗原血症～肝、肾移植术后巨细胞病毒感染监测的分析[J].世界感染杂志,2006,6(1):34-36.
5、张亚光,付庆.对献血者巨细胞病毒感染的研究.河南职工医学院学报,2003,5(4)18-20.
6、张欣文,李芬,史晓薇等.先天性巨细胞病毒感染对无症状患儿生长发育的影响.第三军医大学学报,2006,28(24):2475-2477.
7、陆嘉良,王云飞,刘佩莉.孕妇巨细胞病毒激活感染及对胎儿影响研究.中国公共卫生,2002,18(4):439-441.
8、米荣,徐放生,周丛乐.婴儿巨细胞病毒感染的临床特征.中国新生儿科杂志,2007,22(2):115-117.
9、陈平洋,贺晓日,王涛等.新生儿先天性巨细胞病毒感染的临床研究.实用儿科临床杂志,2007,22(22):1697-1689,1728.
10、李爱斌,刘谦,夏良等,巨细胞病毒感染的致病机制初探.中华实验和临床病毒学杂志,2003,17(4):369-371.
11、罗开军.先天性人巨细胞病毒感染致中枢神经系统发育异常的机制.现代医药卫生,2004,20(2):102-103.
12、李丹.先天性巨细胞病毒感染导致脑组织损伤的研究进展.国外医学病毒学分册,2004,11(6):161-164.
13、杨晶,史湘英,骆萍.更昔洛韦治疗新生儿巨细胞病毒感染66例.航空航天医药,2007,18(2):79-80.
14、赵秀荣,张欢.巨细胞病毒感染的防治研究进展.承德医学院学报,2007,24(2):185-186.
15、王明丽,陈贵海,唐久来等.人巨细胞病毒感染新生乳鼠原代培养脑神经细胞研究.病毒学报,1999,15(2):136-142.
16、柳燕,王明丽,周勇.人巨细胞病毒先天性感染对ICR鼠胚胎生长及脑组织发育的影响.安徽医科大学学报,2001,36(2):98-101.
17、柳燕,王明丽.人巨细胞病毒先天性感染胎鼠大脑皮质的研究.安徽预防医学杂志,2001,7(6):403-404.
18、王明丽,唐久来,胡闻等.人巨细胞病毒先天性中枢神经系统感染小鼠模型的建立.动物学报,2000,46(2):167-174.
19、蔡亦红,高荣保,王明丽.人巨细胞病毒增殖性感染新生乳鼠大脑皮质神经细胞.安徽医科大学 学报,2006,41(3):237-240.
20、周玉峰,方峰.董永绥等.小鼠巨细胞病毒抑制神经干细胞分化及其机制研究.中华儿科杂志,2006,44(7):505-508.
21、周玉峰,方峰,甄宏等.小鼠巨细胞病毒感染神经干细胞的体外研究.中华微生物学和免疫学杂志,2006,26(2):169-173.
22、赵俊,王明丽,陈敬贤.3种方法检测HCMV先天性感染对老年小鼠大脑皮质细胞凋亡的比较.安徽医科大学学报,2007,42(2)157-160.
23、蔡亦红等.人巨细胞病毒感染小鼠大脑皮质细胞的体内外实验研究.安徽医科大学硕士学位论文,2006.
24、 Anthony N.van den Pol,Edward Mocarski,Noah Saederup etal.Cytomegalovirus Cell Tropism,Replication,and Gene Transfer in Brain.The Journal of Neuroscience.1999,19(24):10948-10965.
25、 Isao Kosugi,Yuichiro Shinmura,Hideya Kawasaki etal.Cytomegalovirus Infection of the Central Nervous System Stem Cells from Mouse Embryo:A Model for Developmental Brain Disorders Induced by Cytomegalovirus.Labratory Investigation.2000,80(9):1373-1383.
26、 Yoshihiro Tsutsui,Isao Kosugi,Hideya Kawasaki.Neuropathogenesis in cytomegalovirus infection:Indication of the mechanisms using mouse models.Reviews in Medical Virology,2005,15:327-345.
27、 Kosugi I,Shinmura Y,Li RY etal.Murine cytomegalovirus induces apoptosis in non-infected cells of the developing mouse brain and blocks apoptosis in primary neuronal culture.Acta Neuropathol.1998,96(3):239-247.
28、刘志峰.胚胎和干细胞中的巨细胞病毒感染.国外医学.流行病学传染病学分册,2002,29(2):90-91.
29、 Maxim C.-J.Cheeran,Shuxian Hu,Hsiao T.Ni etal.Neural Precursor Cell Susceptibility to Human Cytomegalovirus Diverges Along Glial or Neuronal Differentiation Pathways.Journal of Neuroscience Research,2005,82:839-850.
30、 James R,Lokensgard,Maxim C.-J.Cheeran,Genya Gekker etal.Human Cytomegalovirus Replication and Modulation of Apoptosis in Astrocytes.Journal of Human Virology,1999,2(2):91-101.
31、李薇,张丽江,仲宁.人巨细胞病毒感染人胚脑神经细胞的形态学研究.临床神经病学杂志,2001,14(1):12-13.
32、 Thomas Hazel,Thomas Muller.Culture of Neuroepithelial stem Cells.Current Protocols in Neuroscience.2001.
33、 Philip H.Schwartz,Peter J.Bryant,Tannin J.Fuja etal.Isolation and Characterization of Neural Progenitor Cells From Post-Mortera Human Cortex.Journal of Neuroscience Research.2003.74:838-851.
34、孙晓红,鲁强,刘玉军等.人胚胎海马神经干细胞体外培养方法的建立.首都医科大学学报,2004,25(2):144-146.
35、梁鹏,卫淑静,徐薇等.人胚神经干细胞体外长期培养系统的建立.中华神经外科疾病研究杂志.2005,4(1):41-43.
36、X U H an-P eng,L IU S hu-J uan,GOU L in等.Establ ishmen t of human embryo neural stem cell l ine in vitro.第四军医大学学报.2001,22(2):185-186.
37、龙慧,王绍闯,蔡芳等.人胚神经干细胞的体外分离培养和长期冻存.中国现代医学杂志.2007,17(6):686-688.
38、陈思源,万虹,历俊华等.人胚神经干细胞的体外培养及鉴定.中华神经外科学杂志.2006,22(10):624-627.
39、赵婷秀,姜霞,王秀莲等.激光共聚焦显微镜观察FITC-AnnexinV/PI双染色法检测人肺癌细胞凋亡.湖北中医学院学报,2005,7(4):9-11.
40、陈刚,秦尚振,马廉亭等.人胚神经干细胞向神经元样细胞诱导分化的研究.Journal of Chinese Physician.2006,8(12):1624-1626.
41、孙鹏,邹春林,董恺等.人胚海马神经干细胞体外培养及分化研究.中华神经外科杂志.2005,21(7):393—397.
42、谭雪锋,金国华,田美玲等.人胚脑神经干细胞的分离培养、克隆和分化.神经解剖学杂志.2004,20(3):262-266.
43、、 Jenny Odeberg.Nina Wolmer.Scott Falci et al.Human Cytomegalovirus Inhibits Neuronal Differentiation and Induces Apoptosis in Human Neural Precursor Cells.Journal of Virology,2006,80(18):8929-8939.
44、 Jenny Odeberg,Nina Wolmer,Scott Falci et al.Late Human Cytomegalovirus(HCMV)Proteins Inhibit Differentiation of Human Neural Precursor Cells Into Astrocytes.Journal of Neuroscience Research,2007,85:583-593.
45、 McCarthy M,Auger D,Whittemore SR et al.Human cytomegalovirus causes productive infection and neuronal injury in differentiating fetal human central nervous system neuroepithelial precursor cells.J Hum Virol,2000,3:215-228.
46、 Eileen M.Burd,Jose S.Pulido,Donald G.Puro etal.Replication of Human Cytomegalovirus in Human Retinal Glial Cells.Investigative Ophthalmology & Visual Science,1996,37(10)1957-1966.
47、罗杰峰,黎海燕,沈岳飞.星形胶质细胞对神经干细胞分化的影响.中国组织工程研究与临床康复,2007,11(42):8515-8519.
48、王西林.神经胶质细胞的功能[J].黔南民族医专学报,2007,20(1):61-62,64.
49、郭瑾,徐群渊.胶质细胞系源性神经营养因子在神经元发育中的生物学功能料[J].中国临床康复,2006,10(18):126-128.
50、 A.Louise McCormick,Linda Roback,Edward S.Mocarski.HtrA2/0mi Terminates Cytomegalovirus Infection and Is Controlled by the Viral Mitochondrial Inhibitor of Apoptosis(vMIA).PLoS Pathogens,2008,4(5):el000063.
51、 Terhune S,Torigoi E,Moorman N etal.Human cytomegalovirus UL38 protein blocks apoptosis.J ournal of Virology.2007,81(7):3109-3123.
52、 Nie X,Fang F,Li H etal.Effects of human cytomegalovirus infection on apoptosis and expression of apoptosis-regulating factors.Journal of Huazhong University of Science and Technology,Medecial Sciences.2005;25(5):480-483.
53、魏国庆、林茂芳、黄河等.人巨细胞病毒对骨髓间充质干细胞的感染及其凋亡诱导作用.中华血液学杂志,2004,25(11):683-685.
54、魏国庆,枯茂芳,黄河等.巨细胞病毒对人胚成纤维细胞骨架的影响及其凋亡诱导作用.病毒学报,2004,20(3):261-265.
55、王德胜,黄从毒,杨波等.HCMV对培养HUVEC凋亡的作用.湖北医科大学学报,2000,21(2):121-123.
56、李晓峰,王清文,何政贤等。人巨细胞病毒体外感染诱导早幼粒细胞白血病细胞凋亡。中国实验血液学杂志,2007,15(1):63-66.
57、洪艳丽.人臣细胞病毒感染对细胞凋亡的研究进展A review on importance of HCMV infection to cell apotosis.中华实用中西医杂志.2008,21(4):296-297.
58、刘志峰.巨细胞病毒感染与细胞凋亡的研究进展.国外医学病毒学分册.2002,9(6):173-176.
1、 PeckhamCS.Cytomegalovirus infection:congenital and neonatal disease.Scand J Infect Dis Suppl,1991,80:82-87.
2、闻玉梅,陆德源,何丽芳等.现代医学微生物学.上海:上海医科大学出版社,1991,925-948.
3、金锐.巨细胞病毒特性综述.科协论坛,2007,7(下):38.
4、张亚光,付庆.对献血者巨细胞病毒感染的研究.河南职工医学院学报,2003,5(4)18-20.
5、王政禄,印志琪,李卉等.HCMV(pp65)抗原血症～肝、肾移植术后巨细胞病毒感染监测的分析[J].世界感染杂志,2006,6(1):34-36.
6、张欣文,李芬,史晓薇等.先天性巨细胞病毒感染对无症状患儿生长发育的影响.第三军医大学学报,2006,28(24):2475-2477.
7、陆嘉良,王云飞,刘佩莉.孕妇巨细胞病毒激活感染及对胎儿影响研究.中国公共卫生,2002,18(4):439-441.
8、米荣,徐放生,周丛乐.婴儿巨细胞病毒感染的临床特征.中国新生儿科杂志,2007,22(2):115-117.
9、陈平洋,贺晓日,王涛等.新生儿先天性巨细胞病毒感染的临床研究.实用儿科临床杂志,2007,22(22):1697-1689,1728.
10/李爱斌,刘谦,夏良等,巨细胞病毒感染的致病机制初探.中华实验和临床病毒学杂志,2003,17(4):369-371.
11、罗开军.先天性人巨细胞病毒感染致中枢神经系统发育异常的机制.现代医药卫生,2004,20(2):102-103.
12、李丹.先天性巨细胞病毒感染导致脑组织损伤的研究进展.国外医学病毒学分册,2004,11(6):161-164.
13、杨晶,史湘英,骆萍.更昔洛韦治疗新生儿巨细胞病毒感染66例.航空航天医药,2007,18(2):79-80.
14、赵秀荣,张欢.巨细胞病毒感染的防治研究进展.承德医学院学报,2007,24(2):185-186.
15、郭红梅.先天性巨细胞病毒感染研究进展.国外医学儿科学分册.2004,31(5):231-233.
16、杨爱景.实时荧光定量PCR在检测孕妇血HCMV感染中的研究.中国优生与遗传杂志.2006,14(1):24-25.
17、刘忐峰.胚胎和干细胞中的巨细胞病毒感染.国外医学.流行病学传染病学分册,2002,29(2):90-91.
18、左约维,赵杨,陈敦金等.人巨细胞病毒负荷量对细胞病变的影响.热带医学杂志.2006,6(4):394-396.
19、陈俊青,刘霆.巨细胞病毒感染检测方法的现况和进展.中国输血杂志.2005,18(5):428-431.
20、吴旗,邹俊煊,虞涛等.血清CMV DNA荧光定量PCR方法的建立与初步应用.华中科技大学学报(医学版).2006,35(2):279-280.
21、余蓉.巨细胞病毒感染的诊断和产前诊断.中国优生与遗传杂志.2006,14(4):118-119.
22、李宏波,李沛,张永乐等.荧光定量聚合酶链反应在巨细胞病毒性肝炎中的应用.医学研究杂志.2008,37(3):125-126.
23、杨晶,史湘英,骆萍.更昔洛韦治疗新生儿巨细胞病毒感染66例.航空航天医药.2007,18(2):79-80.
24、赵秀荣,张欢.巨细胞病毒感染的防治研究进展.承德医学院学报.2007,24(2):185-186.
25、赵宏,范骏,陈晓明等.IE抗原检测在HCMV感染中的诊断意义.浙江检验医学.2008,6(4):34-35.
26、白剑,石炳毅,肖漓等.流式细胞技术检测肾脏移植受者pp65抗原血症的意义.中国组织工程研究与临床康复.2008,12(58):10441-10444.
27、周浩,王毅,王芳等.肾移植术后巨细胞病毒感染的诊治进展.现代生物医学进展.2009,9(2):391-394.
28、谢丹宇,袁转弟,林国敬等.苦参碱注射液治疗婴儿巨细胞病毒性肝炎的疗效观察.实用儿科临床杂志.2008,23(7):524-526.
29、蔡亦红等.人巨细胞病毒感染小鼠大脑皮质细胞的体内外实验研究.安徽医科大学硕士学位论文,2006.
30、王明丽,陈贵海,唐久来等.人巨细胞病毒感染新生乳鼠原代培养脑神经细胞研究.病毒学报,1999,15(2):136-142.
31、柳燕,王明丽,周勇.人巨细胞病毒先天性感染对ICR鼠胚胎生长及脑组织发育的影响.安徽医科大学学报,2001,36(2):98-101.
32、柳燕,王明丽.人巨细胞病毒先天性感染胎鼠大脑皮质的研究.安徽预防医学杂忠,2001,7(6):403-404.
33、王明丽,唐久来,胡闻等.人巨细胞病毒先天性中枢神经系统感染小鼠模型的建立.动物学报,2000,46(2):167-174.
34、、蔡亦红,高荣保,王明丽.人巨细胞病毒增殖性感染新生乳鼠大脑皮质神经细胞.安徽医科大学学报,2006,41(3):237-240.
35、周玉峰,方峰.董永绥等.小鼠巨细胞病毒抑制神经干细胞分化及其机制研究.中华儿科杂志,2006,44(7):505-508.
36、周玉峰,方峰,甄宏等.小鼠巨细胞病毒感染神经干细胞的体外研究.中华微生物学和免疫学杂志,2006,26(2):169-173.
37、赵俊,王明丽,陈敬贤.3种方法检测HCMV先天性感染对老年小鼠大脑皮质细胞凋亡的比较.安徽医科大学学报,2007,42(2)157-160.
38、Anthony N.van den Pol,Edward Mocarski,Noah Saederup etal.Cytomegalovirus Cell Tropism,Replication,and Gene Transfer in Brain.The Journal of Neuroscience.1999,19(24):10948-10965.
39、 Isao Kosugi,Yuichiro Shinraura,Hideya Kawasaki etal.Cytoraegalovirus Infection of the Central Nervous System Stem Cells from Mouse Embryo:A Model for Developmental Brain Disorders Induced by Cytomegalovirus.Labratory Investigation.2000,80(9):1373-1383.
40、 Yoshihiro Tsutsui,Isao Kosugi,Hideya Kawasaki.Neuropathogenesis in cytomegalovirus infection:Indication of the mechanisms using mouse models.Reviews in Medical Virology,2005,15:327-345.
41、 Kosugi I,Shinmura Y,Li RY etal.Murine cytomegalovirus induces apoptosis in non-infected cells of the developing mouse brain and blocks apoptosis in primary neuronal culture.Acta Neuropathol.1998,96(3):239-247.
42、 Thomas Hazel,Thomas Muller.Culture of Neuroepithelial stem Cells.Current Protocols in Neuroscience.2001.
43、 Philip H.Schwartz,Peter J.Bryant,Tannin J.Fuja etal.Isolation and Characterization of Neural Progenitor Cells From Post-Mortem Human Cortex.Journal of Neuroscience Research.2003.74:838-851.
44、孙晓红,鲁强,刘玉军等.人胚胎海马神经干细胞体外培养方法的建立.首都医科大学学报,2004,25(2):144-146.
45、梁鹏,卫淑静,徐薇等.人胚神经干细胞体外长期培养系统的建立.中华神经外科疾病研究杂志.2005,4(1):41-43.
46、X U H an-P eng,L IU S hu-J uan,GOU L in等.Establ ishmen t of human embryo neural stem cell l ine in vitro.第四军医大学学报.2001,22(2):185-186.
47、龙慧,王绍闯,蔡芳等.人胚神经干细胞的体外分离培养和长期冻存.中国现代医学杂志.2007,17(6):686-688.
48、陈思源,万虹,历俊华等.人胚神经干细胞的体外培养及鉴定.中华神经外科学杂志.2006,22(10):624-627.
49、、陈刚,秦尚振,马廉亭等.人胚神经干细胞向神经元样细胞诱导分化的研究.Journal of Chinese Physician.2006,8(12):1624-1626.
50、、孙鹏,邹春林,董恺等.人胚海马神经干细胞体外培养及分化研究.中华神经外科杂志.2005,21(7):393-397.
51、谭雪锋,金国华,田美玲等.人胚脑神经干细胞的分离培养、克隆和分化.神经解剖学杂忐.2004,20(3):262-266.
52、李薇,张丽江,仲宁.人巨细胞病毒感染人胚脑神经细胞的形态学研究.临床神经病学杂志,2001,14(1):12-13.
53、 Maxim C.-J.Cheeran,Shuxian Hu,Hsiao T.Ni etal.Neural Precursor Cell Susceptibility to Human Cytomegalovirus Diverges Along Glial or Neuronal Differentiation Pathways.Journal of Neuroscience Research,2005,82:839-850.
54、 James R,Lokensgard,Maxim C.-J.Cheeran,Genya Gekker etal.Human Cytomegalovirus Replication and Modulation of Apoptosis in Astrocytes.Journal of Human Virology,1999,2(2):91-101.
55、 Jenny Odeberg.Nina Wolmer.Scott Falci et al.Human Cytomegalovirus Inhibits Neuronal Differentiation and Induces Apoptosis in Human Neural Precursor Cells.Journal of Virology,2006,80(18):8929-8939.
56、 Jenny Odeberg,Nina Wolmer,Scott Falci et al.Late Human Cytomegalovirus(HCMV)Proteins Inhibit Differentiation of Human Neural Precursor Cells Into Astrocytes.Journal of Neuroscience Research,2007,85:583-593.
57、 McCarthy M,Auger D,Whittemore SR et al.Human cytomegalovirus causes productive infection and neuronal injury in differentiating fetal human central nervous system neuroepithelial precursor cells.J Hum Virol,2000,3:215-228.
58、 Eileen M.Burd,Jose S.Pulido,Donald G.Puro etal.Replication of Human Cytomegalovirus in Human Retinal Glial Cells.Investigative Ophthalmology & Visual Science,1996,37(10)1957-1966.
59、戴橄,陈利玉,李太存等。HCMV感染人神经胶质瘤细胞的光镜、电镜及免疫组化研究。中华实验和临床病毒学杂志。2007,21,(2):143.
60、 A.Louise McCormick,Linda Roback,Edward S.Mocarski.HtrA2/0mi Terminates Cytomegalovirus Infection and Is Controlled by the Viral Mitochondrial Inhibitor of Apoptosis(vMIA).PLoS Pathogens,2008,4(5):el000063.
61、 Terhune S,Torigoi E,Moorman N etal.Human cytomegalovirus UL38 protein blocks apoptosis.J ournal of Virology.2007,81(7):3109-3123.
62、 Reboredo M,Greaves RF,Hahn G.Human cytomegalovirus proteins encoded by UL37 exon 1 protect infected fibroblasts against virus-induced apoptosis and are required for efficient virus replication.Journal of General Virology 2004,85:3555-3567.
63、陈敦金,赵杨,闻良珍.人巨细胞病毒感染对宿主细胞周期的影响.热带医学杂志.2003,3(4):481-483.
64、文兰.人巨细胞病毒立即早期蛋白功能的研究进展.国际病毒学杂志.2006,13(3):90-94.
65、刘楠,余艳红,钟梅.人巨细胞病毒感染对宿主细胞周期进程影响的实验研究.中华实验和临床病毒学杂志.2007,21(2):162-164.
66、 Nie X,Fang F,Li H etal.Effects of human cytomegalovirus infection on apoptosis and expression of apoptosis-regulating factors.Journal of Huazhong University of Science and Technology,Medecial Sciences.2005:25(5):480-483.
67、魏国庆、林茂芳、黄河等.人巨细胞病毒对骨髓间充质干细胞的感染及其凋亡诱导作用.中华血液学杂志,2004,25(11):683-685.
68、魏国庆,枯茂芳,黄河等.巨细胞病毒对人胚成纤维细胞骨架的影响及其凋亡诱导作用.病毒学报,2004,20(3):261-265.
69、王德胜,黄从毒,杨波等.HCMV对培养HUVEC凋亡的作用.湖北医科大学学报,2000,21(2):121-123.
70、李晓峰,王清文,何政贤等.人巨细胞病毒体外感染诱导早幼粒细胞白血病细胞凋亡.中国实验血液学杂志.2007,15(1):63-66.
71、洪艳丽.人臣细胞病毒感染对细胞凋亡的研究进展A review on importance of HCMV infection to cell apotosis.中华实用中西医杂志.2008,21(4):296-297.
72、刘志峰.巨细胞病毒感染与细胞凋亡的研究进展.国外医学病毒学分册.2002,9(6):173-176.
75、罗杰峰,黎海燕,沈岳飞.星形胶质细胞对神经干细胞分化的影响.中国组织工程研究与临床康复,2007,11(42):8515-8519.
76、王西林.神经胶质细胞的功能[J].黔南民族医专学报,2007,20(1):61-62,64.
2、闻玉梅,陆德源,何丽芳等.现代医学微生物学.上海:上海医科大学出版社,1991,925-948.
3、金锐.巨细胞病毒特性综述.科协论坛,2007,7(下):38.
4、王政禄,印志琪,李卉等.HCMV(pp65)抗原血症～肝、肾移植术后巨细胞病毒感染监测的分析[J].世界感染杂志,2006,6(1):34-36.
5、张亚光,付庆.对献血者巨细胞病毒感染的研究.河南职工医学院学报,2003,5(4)18-20.
6、张欣文,李芬,史晓薇等.先天性巨细胞病毒感染对无症状患儿生长发育的影响.第三军医大学学报,2006,28(24):2475-2477.
7、陆嘉良,王云飞,刘佩莉.孕妇巨细胞病毒激活感染及对胎儿影响研究.中国公共卫生,2002,18(4):439-441.
8、米荣,徐放生,周丛乐.婴儿巨细胞病毒感染的临床特征.中国新生儿科杂志,2007,22(2):115-117.
9、陈平洋,贺晓日,王涛等.新生儿先天性巨细胞病毒感染的临床研究.实用儿科临床杂志,2007,22(22):1697-1689,1728.
10、李爱斌,刘谦,夏良等,巨细胞病毒感染的致病机制初探.中华实验和临床病毒学杂志,2003,17(4):369-371.
11、罗开军.先天性人巨细胞病毒感染致中枢神经系统发育异常的机制.现代医药卫生,2004,20(2):102-103.
12、李丹.先天性巨细胞病毒感染导致脑组织损伤的研究进展.国外医学病毒学分册,2004,11(6):161-164.
13、杨晶,史湘英,骆萍.更昔洛韦治疗新生儿巨细胞病毒感染66例.航空航天医药,2007,18(2):79-80.
14、赵秀荣,张欢.巨细胞病毒感染的防治研究进展.承德医学院学报,2007,24(2):185-186.
15、王明丽,陈贵海,唐久来等.人巨细胞病毒感染新生乳鼠原代培养脑神经细胞研究.病毒学报,1999,15(2):136-142.
16、柳燕,王明丽,周勇.人巨细胞病毒先天性感染对ICR鼠胚胎生长及脑组织发育的影响.安徽医科大学学报,2001,36(2):98-101.
17、柳燕,王明丽.人巨细胞病毒先天性感染胎鼠大脑皮质的研究.安徽预防医学杂志,2001,7(6):403-404.
18、王明丽,唐久来,胡闻等.人巨细胞病毒先天性中枢神经系统感染小鼠模型的建立.动物学报,2000,46(2):167-174.
19、蔡亦红,高荣保,王明丽.人巨细胞病毒增殖性感染新生乳鼠大脑皮质神经细胞.安徽医科大学 学报,2006,41(3):237-240.
20、周玉峰,方峰.董永绥等.小鼠巨细胞病毒抑制神经干细胞分化及其机制研究.中华儿科杂志,2006,44(7):505-508.
21、周玉峰,方峰,甄宏等.小鼠巨细胞病毒感染神经干细胞的体外研究.中华微生物学和免疫学杂志,2006,26(2):169-173.
22、赵俊,王明丽,陈敬贤.3种方法检测HCMV先天性感染对老年小鼠大脑皮质细胞凋亡的比较.安徽医科大学学报,2007,42(2)157-160.
23、蔡亦红等.人巨细胞病毒感染小鼠大脑皮质细胞的体内外实验研究.安徽医科大学硕士学位论文,2006.
24、 Anthony N.van den Pol,Edward Mocarski,Noah Saederup etal.Cytomegalovirus Cell Tropism,Replication,and Gene Transfer in Brain.The Journal of Neuroscience.1999,19(24):10948-10965.
25、 Isao Kosugi,Yuichiro Shinmura,Hideya Kawasaki etal.Cytomegalovirus Infection of the Central Nervous System Stem Cells from Mouse Embryo:A Model for Developmental Brain Disorders Induced by Cytomegalovirus.Labratory Investigation.2000,80(9):1373-1383.
26、 Yoshihiro Tsutsui,Isao Kosugi,Hideya Kawasaki.Neuropathogenesis in cytomegalovirus infection:Indication of the mechanisms using mouse models.Reviews in Medical Virology,2005,15:327-345.
27、 Kosugi I,Shinmura Y,Li RY etal.Murine cytomegalovirus induces apoptosis in non-infected cells of the developing mouse brain and blocks apoptosis in primary neuronal culture.Acta Neuropathol.1998,96(3):239-247.
28、刘志峰.胚胎和干细胞中的巨细胞病毒感染.国外医学.流行病学传染病学分册,2002,29(2):90-91.
29、 Maxim C.-J.Cheeran,Shuxian Hu,Hsiao T.Ni etal.Neural Precursor Cell Susceptibility to Human Cytomegalovirus Diverges Along Glial or Neuronal Differentiation Pathways.Journal of Neuroscience Research,2005,82:839-850.
30、 James R,Lokensgard,Maxim C.-J.Cheeran,Genya Gekker etal.Human Cytomegalovirus Replication and Modulation of Apoptosis in Astrocytes.Journal of Human Virology,1999,2(2):91-101.
31、李薇,张丽江,仲宁.人巨细胞病毒感染人胚脑神经细胞的形态学研究.临床神经病学杂志,2001,14(1):12-13.
32、 Thomas Hazel,Thomas Muller.Culture of Neuroepithelial stem Cells.Current Protocols in Neuroscience.2001.
33、 Philip H.Schwartz,Peter J.Bryant,Tannin J.Fuja etal.Isolation and Characterization of Neural Progenitor Cells From Post-Mortera Human Cortex.Journal of Neuroscience Research.2003.74:838-851.
34、孙晓红,鲁强,刘玉军等.人胚胎海马神经干细胞体外培养方法的建立.首都医科大学学报,2004,25(2):144-146.
35、梁鹏,卫淑静,徐薇等.人胚神经干细胞体外长期培养系统的建立.中华神经外科疾病研究杂志.2005,4(1):41-43.
36、X U H an-P eng,L IU S hu-J uan,GOU L in等.Establ ishmen t of human embryo neural stem cell l ine in vitro.第四军医大学学报.2001,22(2):185-186.
37、龙慧,王绍闯,蔡芳等.人胚神经干细胞的体外分离培养和长期冻存.中国现代医学杂志.2007,17(6):686-688.
38、陈思源,万虹,历俊华等.人胚神经干细胞的体外培养及鉴定.中华神经外科学杂志.2006,22(10):624-627.
39、赵婷秀,姜霞,王秀莲等.激光共聚焦显微镜观察FITC-AnnexinV/PI双染色法检测人肺癌细胞凋亡.湖北中医学院学报,2005,7(4):9-11.
40、陈刚,秦尚振,马廉亭等.人胚神经干细胞向神经元样细胞诱导分化的研究.Journal of Chinese Physician.2006,8(12):1624-1626.
41、孙鹏,邹春林,董恺等.人胚海马神经干细胞体外培养及分化研究.中华神经外科杂志.2005,21(7):393—397.
42、谭雪锋,金国华,田美玲等.人胚脑神经干细胞的分离培养、克隆和分化.神经解剖学杂志.2004,20(3):262-266.
43、、 Jenny Odeberg.Nina Wolmer.Scott Falci et al.Human Cytomegalovirus Inhibits Neuronal Differentiation and Induces Apoptosis in Human Neural Precursor Cells.Journal of Virology,2006,80(18):8929-8939.
44、 Jenny Odeberg,Nina Wolmer,Scott Falci et al.Late Human Cytomegalovirus(HCMV)Proteins Inhibit Differentiation of Human Neural Precursor Cells Into Astrocytes.Journal of Neuroscience Research,2007,85:583-593.
45、 McCarthy M,Auger D,Whittemore SR et al.Human cytomegalovirus causes productive infection and neuronal injury in differentiating fetal human central nervous system neuroepithelial precursor cells.J Hum Virol,2000,3:215-228.
46、 Eileen M.Burd,Jose S.Pulido,Donald G.Puro etal.Replication of Human Cytomegalovirus in Human Retinal Glial Cells.Investigative Ophthalmology & Visual Science,1996,37(10)1957-1966.
47、罗杰峰,黎海燕,沈岳飞.星形胶质细胞对神经干细胞分化的影响.中国组织工程研究与临床康复,2007,11(42):8515-8519.
48、王西林.神经胶质细胞的功能[J].黔南民族医专学报,2007,20(1):61-62,64.
49、郭瑾,徐群渊.胶质细胞系源性神经营养因子在神经元发育中的生物学功能料[J].中国临床康复,2006,10(18):126-128.
50、 A.Louise McCormick,Linda Roback,Edward S.Mocarski.HtrA2/0mi Terminates Cytomegalovirus Infection and Is Controlled by the Viral Mitochondrial Inhibitor of Apoptosis(vMIA).PLoS Pathogens,2008,4(5):el000063.
51、 Terhune S,Torigoi E,Moorman N etal.Human cytomegalovirus UL38 protein blocks apoptosis.J ournal of Virology.2007,81(7):3109-3123.
52、 Nie X,Fang F,Li H etal.Effects of human cytomegalovirus infection on apoptosis and expression of apoptosis-regulating factors.Journal of Huazhong University of Science and Technology,Medecial Sciences.2005;25(5):480-483.
53、魏国庆、林茂芳、黄河等.人巨细胞病毒对骨髓间充质干细胞的感染及其凋亡诱导作用.中华血液学杂志,2004,25(11):683-685.
54、魏国庆,枯茂芳,黄河等.巨细胞病毒对人胚成纤维细胞骨架的影响及其凋亡诱导作用.病毒学报,2004,20(3):261-265.
55、王德胜,黄从毒,杨波等.HCMV对培养HUVEC凋亡的作用.湖北医科大学学报,2000,21(2):121-123.
56、李晓峰,王清文,何政贤等。人巨细胞病毒体外感染诱导早幼粒细胞白血病细胞凋亡。中国实验血液学杂志,2007,15(1):63-66.
57、洪艳丽.人臣细胞病毒感染对细胞凋亡的研究进展A review on importance of HCMV infection to cell apotosis.中华实用中西医杂志.2008,21(4):296-297.
58、刘志峰.巨细胞病毒感染与细胞凋亡的研究进展.国外医学病毒学分册.2002,9(6):173-176.
1、 PeckhamCS.Cytomegalovirus infection:congenital and neonatal disease.Scand J Infect Dis Suppl,1991,80:82-87.
2、闻玉梅,陆德源,何丽芳等.现代医学微生物学.上海:上海医科大学出版社,1991,925-948.
3、金锐.巨细胞病毒特性综述.科协论坛,2007,7(下):38.
4、张亚光,付庆.对献血者巨细胞病毒感染的研究.河南职工医学院学报,2003,5(4)18-20.
5、王政禄,印志琪,李卉等.HCMV(pp65)抗原血症～肝、肾移植术后巨细胞病毒感染监测的分析[J].世界感染杂志,2006,6(1):34-36.
6、张欣文,李芬,史晓薇等.先天性巨细胞病毒感染对无症状患儿生长发育的影响.第三军医大学学报,2006,28(24):2475-2477.
7、陆嘉良,王云飞,刘佩莉.孕妇巨细胞病毒激活感染及对胎儿影响研究.中国公共卫生,2002,18(4):439-441.
8、米荣,徐放生,周丛乐.婴儿巨细胞病毒感染的临床特征.中国新生儿科杂志,2007,22(2):115-117.
9、陈平洋,贺晓日,王涛等.新生儿先天性巨细胞病毒感染的临床研究.实用儿科临床杂志,2007,22(22):1697-1689,1728.
10/李爱斌,刘谦,夏良等,巨细胞病毒感染的致病机制初探.中华实验和临床病毒学杂志,2003,17(4):369-371.
11、罗开军.先天性人巨细胞病毒感染致中枢神经系统发育异常的机制.现代医药卫生,2004,20(2):102-103.
12、李丹.先天性巨细胞病毒感染导致脑组织损伤的研究进展.国外医学病毒学分册,2004,11(6):161-164.
13、杨晶,史湘英,骆萍.更昔洛韦治疗新生儿巨细胞病毒感染66例.航空航天医药,2007,18(2):79-80.
14、赵秀荣,张欢.巨细胞病毒感染的防治研究进展.承德医学院学报,2007,24(2):185-186.
15、郭红梅.先天性巨细胞病毒感染研究进展.国外医学儿科学分册.2004,31(5):231-233.
16、杨爱景.实时荧光定量PCR在检测孕妇血HCMV感染中的研究.中国优生与遗传杂志.2006,14(1):24-25.
17、刘忐峰.胚胎和干细胞中的巨细胞病毒感染.国外医学.流行病学传染病学分册,2002,29(2):90-91.
18、左约维,赵杨,陈敦金等.人巨细胞病毒负荷量对细胞病变的影响.热带医学杂志.2006,6(4):394-396.
19、陈俊青,刘霆.巨细胞病毒感染检测方法的现况和进展.中国输血杂志.2005,18(5):428-431.
20、吴旗,邹俊煊,虞涛等.血清CMV DNA荧光定量PCR方法的建立与初步应用.华中科技大学学报(医学版).2006,35(2):279-280.
21、余蓉.巨细胞病毒感染的诊断和产前诊断.中国优生与遗传杂志.2006,14(4):118-119.
22、李宏波,李沛,张永乐等.荧光定量聚合酶链反应在巨细胞病毒性肝炎中的应用.医学研究杂志.2008,37(3):125-126.
23、杨晶,史湘英,骆萍.更昔洛韦治疗新生儿巨细胞病毒感染66例.航空航天医药.2007,18(2):79-80.
24、赵秀荣,张欢.巨细胞病毒感染的防治研究进展.承德医学院学报.2007,24(2):185-186.
25、赵宏,范骏,陈晓明等.IE抗原检测在HCMV感染中的诊断意义.浙江检验医学.2008,6(4):34-35.
26、白剑,石炳毅,肖漓等.流式细胞技术检测肾脏移植受者pp65抗原血症的意义.中国组织工程研究与临床康复.2008,12(58):10441-10444.
27、周浩,王毅,王芳等.肾移植术后巨细胞病毒感染的诊治进展.现代生物医学进展.2009,9(2):391-394.
28、谢丹宇,袁转弟,林国敬等.苦参碱注射液治疗婴儿巨细胞病毒性肝炎的疗效观察.实用儿科临床杂志.2008,23(7):524-526.
29、蔡亦红等.人巨细胞病毒感染小鼠大脑皮质细胞的体内外实验研究.安徽医科大学硕士学位论文,2006.
30、王明丽,陈贵海,唐久来等.人巨细胞病毒感染新生乳鼠原代培养脑神经细胞研究.病毒学报,1999,15(2):136-142.
31、柳燕,王明丽,周勇.人巨细胞病毒先天性感染对ICR鼠胚胎生长及脑组织发育的影响.安徽医科大学学报,2001,36(2):98-101.
32、柳燕,王明丽.人巨细胞病毒先天性感染胎鼠大脑皮质的研究.安徽预防医学杂忠,2001,7(6):403-404.
33、王明丽,唐久来,胡闻等.人巨细胞病毒先天性中枢神经系统感染小鼠模型的建立.动物学报,2000,46(2):167-174.
34、、蔡亦红,高荣保,王明丽.人巨细胞病毒增殖性感染新生乳鼠大脑皮质神经细胞.安徽医科大学学报,2006,41(3):237-240.
35、周玉峰,方峰.董永绥等.小鼠巨细胞病毒抑制神经干细胞分化及其机制研究.中华儿科杂志,2006,44(7):505-508.
36、周玉峰,方峰,甄宏等.小鼠巨细胞病毒感染神经干细胞的体外研究.中华微生物学和免疫学杂志,2006,26(2):169-173.
37、赵俊,王明丽,陈敬贤.3种方法检测HCMV先天性感染对老年小鼠大脑皮质细胞凋亡的比较.安徽医科大学学报,2007,42(2)157-160.
38、Anthony N.van den Pol,Edward Mocarski,Noah Saederup etal.Cytomegalovirus Cell Tropism,Replication,and Gene Transfer in Brain.The Journal of Neuroscience.1999,19(24):10948-10965.
39、 Isao Kosugi,Yuichiro Shinraura,Hideya Kawasaki etal.Cytoraegalovirus Infection of the Central Nervous System Stem Cells from Mouse Embryo:A Model for Developmental Brain Disorders Induced by Cytomegalovirus.Labratory Investigation.2000,80(9):1373-1383.
40、 Yoshihiro Tsutsui,Isao Kosugi,Hideya Kawasaki.Neuropathogenesis in cytomegalovirus infection:Indication of the mechanisms using mouse models.Reviews in Medical Virology,2005,15:327-345.
41、 Kosugi I,Shinmura Y,Li RY etal.Murine cytomegalovirus induces apoptosis in non-infected cells of the developing mouse brain and blocks apoptosis in primary neuronal culture.Acta Neuropathol.1998,96(3):239-247.
42、 Thomas Hazel,Thomas Muller.Culture of Neuroepithelial stem Cells.Current Protocols in Neuroscience.2001.
43、 Philip H.Schwartz,Peter J.Bryant,Tannin J.Fuja etal.Isolation and Characterization of Neural Progenitor Cells From Post-Mortem Human Cortex.Journal of Neuroscience Research.2003.74:838-851.
44、孙晓红,鲁强,刘玉军等.人胚胎海马神经干细胞体外培养方法的建立.首都医科大学学报,2004,25(2):144-146.
45、梁鹏,卫淑静,徐薇等.人胚神经干细胞体外长期培养系统的建立.中华神经外科疾病研究杂志.2005,4(1):41-43.
46、X U H an-P eng,L IU S hu-J uan,GOU L in等.Establ ishmen t of human embryo neural stem cell l ine in vitro.第四军医大学学报.2001,22(2):185-186.
47、龙慧,王绍闯,蔡芳等.人胚神经干细胞的体外分离培养和长期冻存.中国现代医学杂志.2007,17(6):686-688.
48、陈思源,万虹,历俊华等.人胚神经干细胞的体外培养及鉴定.中华神经外科学杂志.2006,22(10):624-627.
49、、陈刚,秦尚振,马廉亭等.人胚神经干细胞向神经元样细胞诱导分化的研究.Journal of Chinese Physician.2006,8(12):1624-1626.
50、、孙鹏,邹春林,董恺等.人胚海马神经干细胞体外培养及分化研究.中华神经外科杂志.2005,21(7):393-397.
51、谭雪锋,金国华,田美玲等.人胚脑神经干细胞的分离培养、克隆和分化.神经解剖学杂忐.2004,20(3):262-266.
52、李薇,张丽江,仲宁.人巨细胞病毒感染人胚脑神经细胞的形态学研究.临床神经病学杂志,2001,14(1):12-13.
53、 Maxim C.-J.Cheeran,Shuxian Hu,Hsiao T.Ni etal.Neural Precursor Cell Susceptibility to Human Cytomegalovirus Diverges Along Glial or Neuronal Differentiation Pathways.Journal of Neuroscience Research,2005,82:839-850.
54、 James R,Lokensgard,Maxim C.-J.Cheeran,Genya Gekker etal.Human Cytomegalovirus Replication and Modulation of Apoptosis in Astrocytes.Journal of Human Virology,1999,2(2):91-101.
55、 Jenny Odeberg.Nina Wolmer.Scott Falci et al.Human Cytomegalovirus Inhibits Neuronal Differentiation and Induces Apoptosis in Human Neural Precursor Cells.Journal of Virology,2006,80(18):8929-8939.
56、 Jenny Odeberg,Nina Wolmer,Scott Falci et al.Late Human Cytomegalovirus(HCMV)Proteins Inhibit Differentiation of Human Neural Precursor Cells Into Astrocytes.Journal of Neuroscience Research,2007,85:583-593.
57、 McCarthy M,Auger D,Whittemore SR et al.Human cytomegalovirus causes productive infection and neuronal injury in differentiating fetal human central nervous system neuroepithelial precursor cells.J Hum Virol,2000,3:215-228.
58、 Eileen M.Burd,Jose S.Pulido,Donald G.Puro etal.Replication of Human Cytomegalovirus in Human Retinal Glial Cells.Investigative Ophthalmology & Visual Science,1996,37(10)1957-1966.
59、戴橄,陈利玉,李太存等。HCMV感染人神经胶质瘤细胞的光镜、电镜及免疫组化研究。中华实验和临床病毒学杂志。2007,21,(2):143.
60、 A.Louise McCormick,Linda Roback,Edward S.Mocarski.HtrA2/0mi Terminates Cytomegalovirus Infection and Is Controlled by the Viral Mitochondrial Inhibitor of Apoptosis(vMIA).PLoS Pathogens,2008,4(5):el000063.
61、 Terhune S,Torigoi E,Moorman N etal.Human cytomegalovirus UL38 protein blocks apoptosis.J ournal of Virology.2007,81(7):3109-3123.
62、 Reboredo M,Greaves RF,Hahn G.Human cytomegalovirus proteins encoded by UL37 exon 1 protect infected fibroblasts against virus-induced apoptosis and are required for efficient virus replication.Journal of General Virology 2004,85:3555-3567.
63、陈敦金,赵杨,闻良珍.人巨细胞病毒感染对宿主细胞周期的影响.热带医学杂志.2003,3(4):481-483.
64、文兰.人巨细胞病毒立即早期蛋白功能的研究进展.国际病毒学杂志.2006,13(3):90-94.
65、刘楠,余艳红,钟梅.人巨细胞病毒感染对宿主细胞周期进程影响的实验研究.中华实验和临床病毒学杂志.2007,21(2):162-164.
66、 Nie X,Fang F,Li H etal.Effects of human cytomegalovirus infection on apoptosis and expression of apoptosis-regulating factors.Journal of Huazhong University of Science and Technology,Medecial Sciences.2005:25(5):480-483.
67、魏国庆、林茂芳、黄河等.人巨细胞病毒对骨髓间充质干细胞的感染及其凋亡诱导作用.中华血液学杂志,2004,25(11):683-685.
68、魏国庆,枯茂芳,黄河等.巨细胞病毒对人胚成纤维细胞骨架的影响及其凋亡诱导作用.病毒学报,2004,20(3):261-265.
69、王德胜,黄从毒,杨波等.HCMV对培养HUVEC凋亡的作用.湖北医科大学学报,2000,21(2):121-123.
70、李晓峰,王清文,何政贤等.人巨细胞病毒体外感染诱导早幼粒细胞白血病细胞凋亡.中国实验血液学杂志.2007,15(1):63-66.
71、洪艳丽.人臣细胞病毒感染对细胞凋亡的研究进展A review on importance of HCMV infection to cell apotosis.中华实用中西医杂志.2008,21(4):296-297.
72、刘志峰.巨细胞病毒感染与细胞凋亡的研究进展.国外医学病毒学分册.2002,9(6):173-176.
75、罗杰峰,黎海燕,沈岳飞.星形胶质细胞对神经干细胞分化的影响.中国组织工程研究与临床康复,2007,11(42):8515-8519.
76、王西林.神经胶质细胞的功能[J].黔南民族医专学报,2007,20(1):61-62,64.