慢性血栓栓塞性肺动脉高压基因表达谱的研究  

Study of the differential gene expression profiles in chronic thromboembolic pulmonary hypertension

作　　者：李广辉[1] 刘岩[1] 苏丕雄[1] 张希涛[1] 安向光[1] 高杰[1] 顾松[1] 

机构地区：[1]首都医科大学附属北京朝阳医院心外科,北京市100020

出　　处：《中国心血管病研究》2016年第4期370-374,384,共6页Chinese Journal of Cardiovascular Research

基　　金：北京市卫生系统高层次卫生技术人才培养计划（项目编号：2011-3-017）

摘　　要：目的利用基因表达谱芯片研究慢性血栓栓塞性肺动脉高压病变组织中差异表达的基因，从多基因角度研究疾病发生的分子机制。方法选取5例慢性血栓栓塞性肺动脉高压患者的肺动脉内膜组织作为实验组，并选择年龄和性别相匹配的5例肺移植供体的正常肺动脉内膜组织为对照组。分别提取、纯化RNA，反转录为eDNA，与Affymetrix2．0ST基因芯片进行体外杂交，通过扫描信号及数据处理，分析出CTEPH肺动脉内膜的差异基因表达谱，并选择部分基因进行反转录聚合酶链反应（RT—PCR）验证。结果通过对两组基因表达谱比较分析，筛选出有统计学差异的1614个基因。其中880个基因表达上调，734个基因表达下调。筛选出差异最显著的5个上调基因和5个下调基因，RT—PCR验证TBX15、FM03、ITIH3、CHRDLI、ACADL表达与芯片结果符合。结论慢性血栓栓塞性肺动脉高压存在显著的差异基因表达谱，筛选出来的差异基因涉及炎症反应、细胞黏附、血栓形成、平滑肌增殖、血管生成等，而完整的基因功能信息、传导通路、信号网络等，尚需进一步研究。Objective To investigate the differential gene expression profiles in chronic thromboembolic pulmonary hypertension and discuss the pathogenesis by cDNA microarray. Methods Affymetrix Human Gene 2.0 ST microarray was used to examine the geue expression profiles of pulmonary artery endothelial cells from 5 CTEPH patients and 5 healthy controls from donors of lung transplants and matches to the patients with CTEPH. Total RNA was isolated and purified, reverse transcribed to cDNA. cDNA was hybridized to microarrays. The dif- ferential expressed genes were identified to RT-PCR analysis： Results Compared to normal samples, 1614 genes with statistically changes in expression were identified. Of these, 880 genes were upregulated in CTEPH group and 734 were downregnlated. Five genes that were the most significantly upregulated or downregulated according to the P-value and fold change. RT-PCR results of TBX15, FMO3, ITIH3, CHRDL1, ACADL were consistent with gene chip analysis. Conclusion The differential expressed genes in CTEPH most involved in inflammation, dis- turbed thrombolysis, enhanced thrombosis, cell adhesion, smooth muscle proliferation, angiogenesis. However, further studies are requied to identify GO analysis, pathway and signal-net.

关 键 词：肺栓塞 肺动脉高压 基因表达谱 

分 类 号：R654.2[医药卫生—外科学]