猪—猴异种移植动物模型生物匹配性前导实验
发布时间：2019-06-11 18:58
【摘要】：免疫抑制剂的不断问世大大改善了移植后的免疫排斥反应，使临床移植得到了快速的发展。然而供移植器官来源短缺的困难成为目前器官移植界所面临的最大的难题。猪到人异种移植为解决这个问题提供了一个新的方向，但是由于猪和人在进化过程中是远源物种的关系，所以两者在生理、病理以至基因蛋白水平上都存在巨大差异，这必将导致在异种移植中出现比同种异体移植强烈和复杂的排斥反应。揭示异种移植的排斥机制和寻找有效的方法预防与治疗是将异种移植向临床应用推进的重要课题，需要开展大量临床前的基础理论研究。猪-猴的移植模型是研究猪-人异种移植的重要基础。尽管作为受者的猕猴在生物学和生理功能上与人比较接近，但两者间仍然存在一定差异，为了从中得到更有指导意义的结果，有必要了解两物种的基因差异。 本研究使用Illumina Sentrix Human-6全基因表达谱芯片比较了人和猕猴肝脏、脾脏以及外周血的基因表达，实验结果显示：微阵列检测三种组织的结果共有6000多个基因表达。从中选择24个与缺血再灌注损伤相关的基因进行分析，发现两物种间基因表达的一致率是82.36％；52个与免疫相关的基因，一致率是72.92％；30个与细胞周期相关的基因，一致率是87.01％。应用人的基因芯片检测到人与猕猴mRNA表达的一致率是76.98％。结果提示：人与猕猴基因的差异比我们以前想象的大，
[Abstract]:The continuous emergence of immunosuppressants has greatly improved the immune rejection after transplantation and made clinical transplantation develop rapidly. However, the shortage of sources of organ transplantation has become the biggest problem in the field of organ transplantation. Pig-to-human xenotransplantation provides a new direction to solve this problem, but because pigs and humans are distant species in the process of evolution, there are great differences in physiology, pathology and gene protein level, which will lead to stronger and more complex rejection than allotransplantation. To reveal the rejection mechanism of xenotransplantation and to find effective methods to prevent and treat it is an important topic to promote the clinical application of xenotransplantation. A large number of preclinical basic theory research needs to be carried out. The transplantation model of pig-monkey is an important basis for the study of pig-human xenotransplantation. Although the biological and physiological functions of rhesus monkeys are close to those of human beings, there are still some differences between them. In order to get more instructive results, it is necessary to understand the genetic differences between the two species. In this study, Illumina Sentrix Human-6 full gene expression microarray was used to compare the gene expression in liver, spleen and peripheral blood of human and rhesus monkeys. The results showed that there were more than 6000 gene expressions in the three tissues detected by microarray. 24 genes related to ischemia-reperfusion injury were selected for analysis. It was found that the consistent rate of gene expression between the two species was 82.36% 鈮，
本文编号：2497391
[Abstract]:The continuous emergence of immunosuppressants has greatly improved the immune rejection after transplantation and made clinical transplantation develop rapidly. However, the shortage of sources of organ transplantation has become the biggest problem in the field of organ transplantation. Pig-to-human xenotransplantation provides a new direction to solve this problem, but because pigs and humans are distant species in the process of evolution, there are great differences in physiology, pathology and gene protein level, which will lead to stronger and more complex rejection than allotransplantation. To reveal the rejection mechanism of xenotransplantation and to find effective methods to prevent and treat it is an important topic to promote the clinical application of xenotransplantation. A large number of preclinical basic theory research needs to be carried out. The transplantation model of pig-monkey is an important basis for the study of pig-human xenotransplantation. Although the biological and physiological functions of rhesus monkeys are close to those of human beings, there are still some differences between them. In order to get more instructive results, it is necessary to understand the genetic differences between the two species. In this study, Illumina Sentrix Human-6 full gene expression microarray was used to compare the gene expression in liver, spleen and peripheral blood of human and rhesus monkeys. The results showed that there were more than 6000 gene expressions in the three tissues detected by microarray. 24 genes related to ischemia-reperfusion injury were selected for analysis. It was found that the consistent rate of gene expression between the two species was 82.36% 鈮，
本文编号：2497391
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