摘要目的 筛选肝缺血再灌注肺损伤大鼠早期肺组织差异表达的基因并作初步功能分析.方法 在大鼠全肝缺血再灌注肺损伤模型基础上,将12只雄性成熟SD大鼠随机分为2组,采用含22 012个基因的大鼠全基因组寡核苷酸基因芯片,检测损伤组大鼠肺组织差异表达的基因并进行初步功能分析.差异基因又通过RT-PCR验证分别检测了基因PGLYRP1、MMP14、CYP1A1、IL-1B、SLPI与芯片结果的一致性.结果 大鼠全肝缺血30 min再灌注60 min肺损伤模型肺组织存在80个差异表达的基因,其中上调基因48个(21个功能已知)、下调基因32个(9个功能已知).通过对任意选取的基因进行RT-PCR验证发现与芯片结果的一致性较好,基因芯片结果可靠.其中上调基因包括IL-1α、IL-1β、SLPI、MMP9、MMP14、MMP15、TIMPI、PIK3RL、MAPK、NF-KB、JNK等;下调基因包括CYP1A1、NQO1、GSTA3、RETNLA等.大鼠肝缺血再灌注肺损伤早期肺组织异常表达的基因涉及到炎症反应、细胞代谢、转录因子、信号传导、离子通道或受体、细胞骨架等几方面.结论 基因芯片技术是一种全新的检测手段,可筛选出肝缺血再灌注肺损伤后肺组织差异表达的基因并可指导进一步的治疗.

abstractsObjective To examine the early changes in gene expression levels in lung tissues by cDNA microarray using a rat model of total hepatic ischemia reperfusion and to analysis function of the changes. Methods Twelve adult male SD rats weighting 220-250 g were divided randomly into two groups (6 in each group). The rats were sacrificed at end point of the operation and lung tissues were divided into several parts for either microarray analysis or RT-PCR of several genes selected from microarray data. Common change genes were selected from three chips and the final results of microarray analysis were identified by RT-PCR. At last, differentially expressed genes were classified according to their biological functions by cluster analysis. Results Analysis of the results showed those 48 genes up-regulated and 32 genes down-regalated after hepatic ischemia reperfusion lung injury. Only parts of them had we known about the function. Genes significantly up-regnlated were IL-1α, IL-1β, SLPI, MMP9, MMP14, MMP15, TIMP1, PIK3 RL, MAPK, NF-kB, JN K and others. Genes significantly down-regulated were CYP1A1, NQO1, GSTA3, RETNLA and others. Differentially expressed genes were mainly classified into inflammatory reaction, transcription factors, cell metabolism, signals transduction, ion or receptors, cytoskeleton, etc. Conclusions cDNA microarray technique provides a new method for detecting differentially expressed genes in rat lung tissues. Further study may reveal the molecular pathologic mechanism of hepatic ischemia reperfusion lung injury and discern new targets for therapeutic interventions.