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豬—猴異種移植動(dòng)物模型生物匹配性前導(dǎo)實(shí)驗(yàn)

發(fā)布時(shí)間:2019-06-11 18:58
【摘要】:免疫抑制劑的不斷問世大大改善了移植后的免疫排斥反應(yīng),使臨床移植得到了快速的發(fā)展。然而供移植器官來源短缺的困難成為目前器官移植界所面臨的最大的難題。豬到人異種移植為解決這個(gè)問題提供了一個(gè)新的方向,但是由于豬和人在進(jìn)化過程中是遠(yuǎn)源物種的關(guān)系,所以兩者在生理、病理以至基因蛋白水平上都存在巨大差異,這必將導(dǎo)致在異種移植中出現(xiàn)比同種異體移植強(qiáng)烈和復(fù)雜的排斥反應(yīng)。揭示異種移植的排斥機(jī)制和尋找有效的方法預(yù)防與治療是將異種移植向臨床應(yīng)用推進(jìn)的重要課題,需要開展大量臨床前的基礎(chǔ)理論研究。豬-猴的移植模型是研究豬-人異種移植的重要基礎(chǔ)。盡管作為受者的獼猴在生物學(xué)和生理功能上與人比較接近,但兩者間仍然存在一定差異,為了從中得到更有指導(dǎo)意義的結(jié)果,有必要了解兩物種的基因差異。 本研究使用Illumina Sentrix Human-6全基因表達(dá)譜芯片比較了人和獼猴肝臟、脾臟以及外周血的基因表達(dá),實(shí)驗(yàn)結(jié)果顯示:微陣列檢測(cè)三種組織的結(jié)果共有6000多個(gè)基因表達(dá)。從中選擇24個(gè)與缺血再灌注損傷相關(guān)的基因進(jìn)行分析,發(fā)現(xiàn)兩物種間基因表達(dá)的一致率是82.36%;52個(gè)與免疫相關(guān)的基因,一致率是72.92%;30個(gè)與細(xì)胞周期相關(guān)的基因,一致率是87.01%。應(yīng)用人的基因芯片檢測(cè)到人與獼猴mRNA表達(dá)的一致率是76.98%。結(jié)果提示:人與獼猴基因的差異比我們以前想象的大,
[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,

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