子痫前期重度患者孕16~20周外周血白细胞差异基因的表达及意义  

Different gene expressions in patients with severe preeclampsia

作　　者：徐丽南[1] 王子莲[1] 张颖[1] 蔡坚[1] 杨建波[1] 周灿权[1] 

机构地区：[1]中山大学附属第一医院妇产科,广州510080

出　　处：《中华围产医学杂志》2011年第7期390-395,共6页Chinese Journal of Perinatal Medicine

基　　金：基金项目：广东省科技计划项目（20108031600313）

摘　　要：目的研究子痫前期重度（severepreeclampsia，SPE）患者孕16～20周外周血白细胞的基因表达谱，寻找其外周血白细胞的差异表达基因，为早期预测该疾病的发生发展提供依据。方法采用巢式病例对照研究。选择2008年8月至12月在中山大学附属第一医院产前检查且经B超确定孕周为16~20周的初产妇共800例，随访至妊娠结束。以最终发展为SPE的6例患者为SPE组，40例正常妊娠妇女为对照组，应用人类全基因组cDNA单荧光芯片检测2组孕妇在孕16～20周时外周血白细胞差异基因表达谱。结果SPE组和对照组存在差异表达基因，筛选得到983个差异表达基因，其中719个基因表达上调，264个基因表达下调。SPE组上调基因主要参与免疫相关、凝血纤溶、细胞传导、细胞黏附、转录及蛋白合成，其中血小板T细胞活化抗原1（plateletandTcellactivationantigen1，PTAl／CD226）、杀菌／通透性增加蛋白（bactericidal／permeabilityincreasingprotein，BPI）、白细胞介素-8（interleukin-8，IL-8）、蛋白激酶C（proteinkinaseC，PKC）、淋巴细胞抗原75、黏蛋白（mucoprotein）、表皮生长因子受体通路底物8均明显升高；下调基因主要参与细胞凋亡、钙代谢、脂代谢、细胞转化，其中肾上腺髓质素（adrenomedullin，ADM）、免疫球蛋白样受体（killercellimmunoglobulin-likereceptors，KIR）、维生素D受体（vitaminDreceptor，VDR）、脂肪分化相关蛋白基因、甲状旁腺激素、有丝分裂素激活蛋白激酶激酶4（mitogen-activatedproteinkinasekinase4，MKK4）均明显下降。结论SPE患者外周血白细胞的基因表达在孕16～20周时与正常妊娠存在明显差异，CD226、BPI、IL-8、PKC、ADM、KIR、VDR等基因可能参与SPE的发病，需进一步研究验证。Objective To investigate gene expression profile in peripheral leucocytes of patients with severe preeclampsia （SPE） during 16-20 gestational weeks to see if there are different expression between normal pregnancy and SPE, and to provide the evidence for predicting the pathogenesis of preeclampsia in the future. Methods Eight hundred primipara who accepted pregnancy examination at the First Affiliated of Hospital SUN YAT-SEN University from August 2008 to December 2008 were selected into this study. The gestational age of all objects were confirmed as 16-20 weeks by ultrasonography. And they were followed up until delivered. Six patients developed severe preeclampsia （SPE group）; and 40 pregnant women without any complications were chosen as the control. Human genome complementary DNA （cDNA） single-fluorescent chip were used to detect the different gene expression in peripheral leucocytes between normal pregnancy and SPE at 16-20 gestation weeks. Results There were different expressions in 983 genes between SPE group and control group, among which 719 genes were up-regulated and 264 genes were down-regulated in the SPE group. Up-regulating genes mainly involved in immunity, coagulation and fibrinolysis, signal transduction, cell adhesion, transcription and protein synthesis; and the expression of platelet and T cell activation antigen 1 （ PTA1/CD226 ）, bactericidal/permeability increasing protein （ BPI）,interleukin-8 （IL-8）, protein kinase C （PKC）, lymphocyte antigen 75 （LY-75）, mucoprotein and EGFR pathway substrate 8 （EPSS） were significantly increased in SPE patients. Down regulating genes mainly involved in apoptosis, calcium metabolism, lipid metabolism and ceil transformation; and the expression of adrenomedullin （ADM）, killer cell immunoglobulin-like receptors （KIR）, vitamin D receptor （VDR）, adipose differentiation-related protein （ADRP）, parathyroid hormone （PTH） and mitogen-activated protein kinase kinase 4 （MKK4） were significantIy decreased i

关 键 词：高血压 妊娠期 妊娠初期 DNA 互补 寡核苷酸序列分析 白细胞 基因表达 

分 类 号：R714.245[医药卫生—妇产科学]