肺移植后闭塞性细支气管炎移植物基因表达

Gene expression profile in chronic rejected transplant lungs detected by microarray

目的探讨肺移植后闭塞性细支气管炎（OB）的发病机制。方法建立小鼠异位气道移植OB模型，实验组：同种异体移植组，对照组：同系移植组。观察术后5、15和25d时移植气道病理学改变，利用CSME-80鼠cDNA芯片检测15d时移植物基因表达水平，获得表达谱，并进行生物分析。结果OB前期存在大量基因表达变化，在两个通道均为有效的杂交信号中，上调表达的有422个，主要涉与细胞生存相关的基因类型。结论肺移植后OB是多因素参与的动态不平衡过程。大量基因与细胞生存相关，免疫性因素相对较少，提示潜在的肺移植OB治疗策略的转变。

Objective To investigate the pathogenesis of obliterative bronchiolitis （OB） following lung transplantation. Methods Heterotopic tracheal transplantation model was created. Tracheal grafts were harvested on the day 5,15, and 15, and pathological changes were observed in one half over time, and the other half were subjected to microarray analyses to examine changes in gene expression patterns on the day 15. Results Compared with the isograft control, expression levels of 422 genes were up-regulated in the allograft. A large proportion of the up-regulated genes in this transplant-associated profile were functionally linked with cell survival and differentiation. Conclusion OB presented as a multistage, ongoing and nonequilibrium process. The analyses with much more genes associated with cell differentiation and less with immunological cells suggest the development of new therapeutic strategies.