CTLA4Ig基因修饰人肝细胞株L02诱导免疫耐受的实验研究
发布时间:2021-02-07 19:52
肝细胞移植是治疗肝衰竭和代谢性肝病的重要手段之一,相对于肝脏移植,肝细胞移植具有来源较广、费用相对低廉、创伤较小等优点,可提供暂时性肝功能支持,为肝脏重建创造机会。但同肝移植一样,排斥反应影响移植肝细胞的长期存活和远期疗效。目前解决排斥反应的主要策略是使用免疫抑制剂,但此类药物毒副作用较大,需长期甚至终身使用,且增加感染和肿瘤的发生率。在此背景下,诱导移植物免疫耐受成为研究热点。细胞毒性T淋巴细胞相关抗原4免疫球蛋白(cytotoxic T-lymphocyte associated antigen 4-immunoglobulin, CTLA4Ig)是CTLA4分子胞外功能区与免疫球蛋白IgG恒定区相结合的融合性可溶性蛋白,可与T淋巴细胞表面的CD28分子竞争性结合抗原递呈细胞(antigen presenting cell, APC)表面的B7分子,阻断T细胞活化的共刺激通路,抑制T细胞活化,诱导对特异性抗原的免疫耐受。大量实验已经证实CTLA4Ig可以有效抑制排斥反应,延长移植物存活时间,肝细胞移植中应用CTLA4Ig同样被证实可有效诱导免疫耐受。其主要应用方法为CTLA4Ig蛋...
【文章来源】:中国人民解放军陆军军医大学重庆市
【文章页数】:65 页
【学位级别】:硕士
【部分图文】:
Ad-CTLA4Ig-EGFP转染L02后6h荧光(倒置荧光显微镜×400)
Ad-CTLA4Ig-EGFP转染L02后12h荧光(倒置荧光显微镜×400)
Ad-CTLA4Ig-EGFP转染L02后24h荧光(倒置荧光显微镜×400)
【参考文献】:
期刊论文
[1]基于肝切除手术来源的成人肝细胞移植的临床应用[J]. 李灼日,毛先海,胡小萱,聂盛丹,石咏中,向华,吴金术,陈海鸥,杨建辉,曹友德. 中国现代手术学杂志. 2009(04)
[2]Immunological inhibition of transplanted liver allografts by adeno-associated virus vector encoding CTLA4Ig in rats[J]. Sen Lu, Yue Yu, Yun Gao, Guo-Qiang Li and Xue-Hao Wang Center of Liver Transplantation, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. Hepatobiliary & Pancreatic Diseases International. 2008(03)
[3]AAV体外介导hCTLA4-Ig在新生猪胰岛细胞中的表达与生物学活性[J]. 莫朝晖,王维,刘涛,曾秋华,吴小兵,谢艳红. 中南大学学报(医学版). 2007(01)
[4]Stable Skin-specific Overexpression of Human CTLA4-Ig in Transgenic Mice through Seven Generations[J]. Yong WANG~1 Yong NI~(1,3) Hong WEI~1* Feng-Chao WANG~2 Liang-Peng GE~1 Xiang GAO~41 Department of Animal Science,College of Basic Medicine,Third Military Medical University,Chongqing 400038,China;2 Institute of Combined Injury,College of Military Preventive Medicine,Third Military Medical University,Chongqing 400038,China;3 School of Life Sciences,Southwest University,Chongqing 400715,China;4 Animal Model Research Institute,Nanjing University,Nanjing 210093,China. Acta Biochimica et Biophysica Sinica. 2006(03)
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[6]CTLA4-Ig诱导大鼠同种肝细胞移植免疫耐受的实验研究[J]. 谭屾,赵浩亮. 山西医科大学学报. 2005(05)
[7]大鼠供心转染CTLA4-Ig基因抑制心脏移植后排斥反应[J]. 陈栋,沈世乾,李锦文,曹荣华,郭晖,张伟杰,陈实. 中华器官移植杂志. 2005(08)
[8]同种肝移植大鼠转染融合基因人CTLA4-Ig抑制急性排斥反应[J]. 朱斌,杨甲梅,钱其军,王孟龙,崔贞福,李玲芳,吴孟超. 中华器官移植杂志. 2005(04)
[9]Adenovirus-mediated CTLA4Ig gene inhibits infiltration of immune cells and cell apoptosis in rats after liver transplantation[J]. Guo-Ping Jiang, Zhen-Hua Hu, Shu-Sen Zheng, Chang-Ku Jia, Ai-Bin Zhang, Wei-Lin Wang, Department of Hepatobiliary Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. World Journal of Gastroenterology. 2005(07)
[10]腺病毒介导CTLA4-FasL基因转移诱导大鼠心脏移植物长期存活的作用[J]. 金永柱,王光明,李爱玲,谢蜀生. 中华医学杂志. 2003(22)
本文编号:3022739
【文章来源】:中国人民解放军陆军军医大学重庆市
【文章页数】:65 页
【学位级别】:硕士
【部分图文】:
Ad-CTLA4Ig-EGFP转染L02后6h荧光(倒置荧光显微镜×400)
Ad-CTLA4Ig-EGFP转染L02后12h荧光(倒置荧光显微镜×400)
Ad-CTLA4Ig-EGFP转染L02后24h荧光(倒置荧光显微镜×400)
【参考文献】:
期刊论文
[1]基于肝切除手术来源的成人肝细胞移植的临床应用[J]. 李灼日,毛先海,胡小萱,聂盛丹,石咏中,向华,吴金术,陈海鸥,杨建辉,曹友德. 中国现代手术学杂志. 2009(04)
[2]Immunological inhibition of transplanted liver allografts by adeno-associated virus vector encoding CTLA4Ig in rats[J]. Sen Lu, Yue Yu, Yun Gao, Guo-Qiang Li and Xue-Hao Wang Center of Liver Transplantation, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. Hepatobiliary & Pancreatic Diseases International. 2008(03)
[3]AAV体外介导hCTLA4-Ig在新生猪胰岛细胞中的表达与生物学活性[J]. 莫朝晖,王维,刘涛,曾秋华,吴小兵,谢艳红. 中南大学学报(医学版). 2007(01)
[4]Stable Skin-specific Overexpression of Human CTLA4-Ig in Transgenic Mice through Seven Generations[J]. Yong WANG~1 Yong NI~(1,3) Hong WEI~1* Feng-Chao WANG~2 Liang-Peng GE~1 Xiang GAO~41 Department of Animal Science,College of Basic Medicine,Third Military Medical University,Chongqing 400038,China;2 Institute of Combined Injury,College of Military Preventive Medicine,Third Military Medical University,Chongqing 400038,China;3 School of Life Sciences,Southwest University,Chongqing 400715,China;4 Animal Model Research Institute,Nanjing University,Nanjing 210093,China. Acta Biochimica et Biophysica Sinica. 2006(03)
[5]基因修饰人骨髓间充质干细胞作为骨组织工程种子细胞异种移植的实验研究[J]. 代飞,吴军,许建中,王序全,陈烯伟,贺伟峰. 中华创伤杂志. 2005(11)
[6]CTLA4-Ig诱导大鼠同种肝细胞移植免疫耐受的实验研究[J]. 谭屾,赵浩亮. 山西医科大学学报. 2005(05)
[7]大鼠供心转染CTLA4-Ig基因抑制心脏移植后排斥反应[J]. 陈栋,沈世乾,李锦文,曹荣华,郭晖,张伟杰,陈实. 中华器官移植杂志. 2005(08)
[8]同种肝移植大鼠转染融合基因人CTLA4-Ig抑制急性排斥反应[J]. 朱斌,杨甲梅,钱其军,王孟龙,崔贞福,李玲芳,吴孟超. 中华器官移植杂志. 2005(04)
[9]Adenovirus-mediated CTLA4Ig gene inhibits infiltration of immune cells and cell apoptosis in rats after liver transplantation[J]. Guo-Ping Jiang, Zhen-Hua Hu, Shu-Sen Zheng, Chang-Ku Jia, Ai-Bin Zhang, Wei-Lin Wang, Department of Hepatobiliary Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. World Journal of Gastroenterology. 2005(07)
[10]腺病毒介导CTLA4-FasL基因转移诱导大鼠心脏移植物长期存活的作用[J]. 金永柱,王光明,李爱玲,谢蜀生. 中华医学杂志. 2003(22)
本文编号:3022739
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