小鼠肺移植慢性排斥反应模型移植气道中基因差异表达研究

Gene expression profile of obliterative airway in a mouse heterotopic tracheal transplantation model

目的应用基因芯片技术分析肺移植后闭塞性细支气管炎(OB)形成前期移植气道的基因表达谱。方法首先建立小鼠异位气道移植OB模型,BALB/c小鼠气道异位移植到C57BL/6小鼠(同种异体移植组)或(同系移植组)背部皮下。分别在术后5、15和25d取出移植气道检测形态学改变,并利用CSME-80鼠cDNA芯片检测15d时两组移植物内基因表达差异,分析具有统计学意义的基因表达和OB发病的关系。结果OB前期存在大量基因表达变化,在2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,提示可能的肺移植OB治疗策略的转变。

[Objective] To analyze the gene expression profile in obliterative bronchiolitis following lung transplantation in a mouse heterotopic tracheal transplantation model. [Methods] Heterotopic tracheal transplantation was performed using BALB/c as donors and BALB/c or C57BL/6 as recipients. Tracheal grafts were harvested on day 5, 15 and 15 days and pathological changes were analyzed in one half over time, and the other half were subjected to microarray analyses to examine changes in gene expression patterns at day 15 （preOB period）. [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. [Conclusions] OB presented as a multistage, ongoing and nonequilibrium process. The analysis with mueh more genes associated with cell differentiation and less with immunological cells suggest the development of new therapeutic strategies perhaps requires a paradigm shift away from alloimmunity and inflammation toward one of tissue remodeling and myofibroblast transdifferentiation.