中文摘要：

目的利用基因芯片技术观察室间隔缺损（VSD）胎儿心肌组织基因谱表达的变化,对其可能的分子机制进行初步分析。方法病例组为孕中期VSD胎儿,对照组为同胎龄无心脏畸形的难免流产的胎儿,取胎儿心室心肌组织,提取其总RNA,采用安捷伦4×44k人全基因组表达谱芯片观察其心肌组织基因表达谱的变化,对基因芯片数据进行处理和生物信息学分析,差异基因信号通路分析,并用实时PCR方法验证芯片结果。结果芯片筛选发现VSD胎儿心肌组织与正常胎儿心肌组织差异表达基因1 490个,表达差异2倍、3倍、4倍以上的基因数分别为1 314个、157个、19个;信号通路分析差异基因得到18个具有统计学意义的信号通路,其中包括与心脏发育密切相关的信号通路,如：Notch、PI3K/AKT、MAPK信号通路;随机挑选表达差异的5个基因进行验证,结果表明定量PCR检查结果与芯片筛选结果基本相符。结论 VSD胎儿心肌组织与正常胎儿心肌组织差异表达基因与心脏发育密切相关的信号通路（Notch、PI3K/AKT、MAPK信号通路）有关,这为先天性心脏病发生机制的研究奠定了良好的基础。

英文摘要：

Objective To screen and identify genes in myocardial tissue of fetus with ventricular septal defect（VSD） by using human genome microarray,and analyze the possible mechanism. Methods The fetuses with VSD in the second trimester were included in the experimental group.The control group was chosen from the fetus of inevitable abortion without cardiac malformations.The fetal myocardial tissues were acquired and RNA was extracted and processed.The Agilent 4×44k human genome microarrays were applied to get the data about gen expression changes,the data were analyzed by bioinformatics methods,pathway-express analysis.Differential expressions of genes were certificated by real-time polymerase chain reaction（PCR）. Results One thousand and four hundred ninty genes were found significantly diffe-rentially expressed between fetal VSD myocardium and normal myocardium,1 314,157,19 genes were over 2,3 and 4 folds respectively.The pathway-express analysis indicated that 18 signaling pathway played important roles in the occurrence of fetal VSD,including signaling pathways for heart development,such as： Notch, phosphatidylinositol 3-kinases/v-akt murine thymoma viral oncogene homolog（PI3K/AKT）,mitogen-activated protein kinase（MAPK） signaling pathway.Five genes were randomly selected and verified by real-time PCR,the results of quantitative PCR were basically consistent with the microarray results. Conclusions The differentially expressed genes between fetal VSD myocardium and normal myocardium were related to signaling pathways for heart development（Notch,PI3K/AKT,MAPK signaling pathway）,which pave the way for further studies on the occurrence and development of fetal VSD.