摘要
目的筛选和比较重度子痫前期患者和正常孕妇外周血中差异表达的基因，并分析其表达情况及分子功能。方法应用基因微阵列技术，采用人类全基因组寡核苷酸芯片检测6例重度子痫前期患者（重度子痫前期组）和5例正常孕妇（对照组）外周血中的差异表达基因，分别计算重度子痫前期组6例患者的芯片信号值与对照组混合血芯片的信号值比值；以芯片的信号值比值t〉2．0或≤0．5，且其q_value〈5．4％的标准来确定差异表达基因，层次聚类分析后用GeneOntology软件确定这些基因所属的功能群。结果筛选得到140个差异表达基因，其中86个基因表达上调，54个基因表达下调。重度子痫前期组上调基因主要参与半胱氨酸代谢、鸟氨酸循环、蛋白酶体、转化生长因子（TGF）B信号传导途径，其中钙联蛋白2（CNN2）、基质金属肽酶8（MMP8）、含V—set和免疫球蛋白域4（VSIG4）、蛋白酶体26S亚单位ATPase5（PSMC5）的信号值比值均明显升高；下调基因主要参与自然杀伤细胞介导的细胞毒性作用、抗原呈递作用、细胞色素芳香化酶（P450）代谢途径，其中杀伤细胞免疫球蛋白样受体三域长细胞质尾2（KIR3DL2）、醇醛酮还原酶家族1成员C3（AKR1C3）、含Churchill域1（CHURC1）、溶质载体家族25成员13（SLC25A13）的信号值比值均明显下降。结论重度子痫前期患者外周血的基因表达与正常孕妇存在着很大的差异；CNN2、MMP8、VSIG4、PSMC5、KIR3DL2、AKR1C3、CHURC1、SLC25A13等基因可能参与重度子痫前期的发病机制，需进一步验证。
Objective To investigate genes involved in the mechanisms underlying the progression of severe preeclampsia. Methods We conducted a muhiregional gene expression analysis using peripheral leucocytes from patients with preeclampsia and normal controls. Total RNA was extracted from peripheral blood of six severe preeelampsia and five normotensive pregnancies. We performed genome-wide expression profiling using Affymetrix HG_U133 plus 2.0 chips to screen out differentially expressed genes of 2 fold or more and q_value 〈 5.4%. Using Gene Ontology we identified the function of differentially expressed genes after cluster analysis. Results Among the 47 000 genes that were screened in the microarray, 140 genes were found to be differentially expressed between normal and preeclamptic pregnancies. Eighty six up-regulated candidate genes were mainly involved in cysteine metabolism urea cycle and metabolism of amiogroups, proteasome, TGF-beta signaling pathway, and the ratio of calponin2 （CNN2）, matrix metallopeptidase 8 （ MMP8 ） , V-set and immunoglobulin domain containing 4 （ VSIG4 ） , proteasome 26S subunit ATPase 5 （ PSMC5 ） was evidently increased in preeelampsia patients. Among 54 down-regulated candidates, natural killer cell mediated eytotoxicity, antigen processing and presentation, metabolism of xenobiotics by cytochrome t）450 were the main pathways. KIR3DL2, AKR1C3, CHURC1 and SLC25A13 were obviously decreased in preeclampsia patients. Conclusions The gene expression of peripheral leucocytes in preeclampsia patients is significantly different from that of uncomplicated pregnancies. CNN2, MMPS, VSIG4, PSMC5, KIR3DL2, AKR1C3, CHURC1 and SLC25A13 may be involved in the molecular mechanisms underlying the progression of severe preeclampsia.
出处
《中华妇产科杂志》
CAS
CSCD
北大核心
2008年第9期651-656,共6页
Chinese Journal of Obstetrics and Gynecology
基金
国家自然科学基金（30672238）
关键词
先兆子痫
妊娠
寡核苷酸序列分析
基因表达
Pre-eclampsia
Pregnancy
Oligonucleotide array sequence analysis
Gene expression
