大鼠肾移植急性排斥反应时移植物中基因表达的研究

目的全面认识肾移植急性排斥反应早期移植物内基因表达改变，为进一步探讨肾移植急性排斥反应的发病机理、寻找早期诊断指标提供实验依据。方法以F344大鼠为供者，近交系Lewis大鼠为受者，建立大鼠原位肾移植急性排斥反应模型（同种异体移植组），以近交系Lewis大鼠间肾移植为对照（近交系移植组）。观察术后3、7和14d时的移植肾组织病理学改变，并利用基因芯片技术检测7d时移植物中基因表达水平，获得其表达谱。结果急性排斥反应早期存在大量基因变化，在丽个通道均有有效杂交信号的基因中，上调的有48条，其中7于扰素诱导GTP酶基因上调最为显著。结论移植物排斥反应是个多途径连续衍变的动态不平衡过程，诸多促进排斥与保护因子并存，很难以单一标志物对肾移植急性排斥反应进行早期诊断，但同时通过多个标志物来综合分析还是有一定可能性的。

Gene expression profile in acute rejected transplant kidneys detected by microarray

Objective To investigate the gene expression profile in acute allograft rejection of renal transplantation and provide experimental data for bringing out the mechanisms and finding the markers for early diagnosis of acute rejection. Methods Heterotopic kidney transplantation was performed using F344 or Lewis donors and Lewis recipients. No immunosuppression was used. Graft kidneys were harvested on the day 3, 7 and 14. Pathological changes of the isograft and allograft were compared at different time points. A commercial microarray was used to detect the gene expression levels in grafts at 7th day. Results The expression levels of 48 genes were up-regulated in the allograft in comparison with the isograft control. Interferon 7 induced GTPase was the most significantly upregulated gene in allografts. Conclusion Many pathways might be involved in organ transplant rejection that is a dynamic, nonequilibrium and continuous process. It seems that there is little probability to make early diagnosis with a single marker, but it could yet be done with a cluster of gene markers.