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人α-半乳糖苷酶转导克服异种移植HAR的小鼠实验研究 被引量:4

Inhibition of Hyperacute Rejection by Human α-Galactosidase Gene Transfering in Mice
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摘要 α 半乳糖苷酶可以特异地清除半乳糖α 1,3 半乳糖抗原 (Galα1,3Galantigen) ,此抗原是引起异种器官移植超急性排斥反应 (HyperacuteRejection ,HAR)的主要异种抗原 .将构建好的α半乳糖苷酶转基因载体通过显微注射的方式注入小鼠受精卵 ,培育出了转基因小鼠 .结果表明 ,转基因小鼠的心、肝、肾、脾、肺组织中均有人α 半乳糖苷酶基因的表达 ,其表达可以有效减少小鼠器官表面Galα1,3Gal抗原的表达水平 ,可以降低转基因小鼠脾细胞对补体介导的杀伤作用的敏感性 .研究表明人源α半乳糖苷酶基因可用于研制不表达Galα1,3Gal抗原的转基因动物 ,从而可以降低异种器官移植HAR的反应强度 。 Galactosidase could effectively reduce Galα1,3Gal antigen, which was thought to be the major xenogenic antigen involved in hyperacute rejection (HAR) of xenotransplantation. The transgenic DNA fragments containing α galactosidase gene were micro injected into fertilized eggs of mice and α galactosidase transgenic mice were obtained. Human α galactosidase gene was expressed in most organs of transgenic mice including heart, liver, kidney, lung and spleen. The overexpression of human α galactosidase could greatly reduce the amount of Galα1,3Gal antigens on these organs and attenuated susceptibility of spleen cells to human antibody mediated lysis. The results suggested that human α galactosidase gene could be used to generate transgenic pig with negligible levels of cell surface Galα1,3Gal antigens, thereby having no reactivity with human serum and improving graft survival.
出处 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2003年第3期332-337,共6页 Chinese Journal of Biochemistry and Molecular Biology
基金 北京市科委首都"二四八"重大创新工程项目 (No.95 5 0 2 14 5 0 0 )资助~~
关键词 人α-半乳糖苷酶 转导 异器官移植 超急性排斥反应 3-半乳糖抗原 galactosidase, Galα1,3Gal antigen, xenotransplantation, hyperacute rejection
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参考文献11

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共引文献9

同被引文献39

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