【作者】 孙波；

【导师】 张为远；

【作者基本信息】 吉林大学 ， 妇产科学， 2006， 博士

【摘要】 子痫前期是妊娠期严重并发症之一,病因和发病机制不明,其相关基因的分离是当前研究的热点,也是从分子水平探讨子痫前期发病的重要环节。本文首次运用基因微阵列技术,采用人类全基因组Oligo芯片,对子痫前期外周血白细胞基因进行平行、大规模、高通量的分析,研究子痫前期患者外周血差异表达基因,以寻找差异基因与子痫前期发病机制之间可能的内在联系。子痫前期组和正常妊娠对照组外周血白细胞表达谱芯片微阵列分析结果发现:子痫前期组和正常妊娠组存在差异表达基因316个,子痫前期组差异表达上调基因120个,下调基因196个,这些基因涉及细胞代谢、信号传导、运输、转录调控、细胞增殖和凋亡等方面的功能。其中,一部分基因是以往的研究己经发现与子痫前期发病相关的基因,同时本研究也发现了一系列以往未报道过的基因在子痫前期外周血中的变化。本研究初步得到了子痫前期外周血白细胞基因表达谱,发现了一批与子痫前期发病及病理生理相关的基因,并验证了基因芯片在子痫前期研究中应用的可行性。这些差异表达基因涉及到多方面细胞功能,提示子痫前期的发生可能涉及多种基因分子机制。研究这些基因在子痫前期外周血的差异表达,了解子痫前期在细胞增殖、应激反应、信号传导、凋亡、运输和代谢,以及基因合成、修复和调控等方面的变化,将为阐明子痫前期发病机制和病理生理环节提供新的研究线索和途径。此外,研究基因表达谱还对未报道的基因功能提供实验依据,对新基因功能的开发具有高度的指导意义。更多还原

【Abstract】 Preeclampsia is one of the common complications of pregnancy, which is the leading cause of perinatal morbidity and mortality. However its real patho-physiological process has remained unknown after intensive studies for more than a century. The possible reason maybe involve immune dysfunction initiated by inherited factors, which lead to trophocyte infiltration disability, endothelial cell injury, releasing of vescular-active substance, which result in arteriole spasm and preeclampsia ultimately. So, the etiology and pathogenesis of preclampsia are not one gene or protein abnormality, but possibly involve in a series of gene and protein changes. It is necessary to investigate the etiology of preeclampsia thoroughly with new approach which can provide new clue for the study of preclampsia.Gene expression detection with Gene microarray and real-time PCR technique has been widely applied in recent years, which as a new bio-technology play an important role in the etiology and molecular diagnosis. The isolation of preeclampsia associated gene is the hot spot of current research, which also is key link for the investigation of pre-eclampsia etiology for molecular level. Till now, little is known for the gene expression change of pre-eclampsia etiology process, so it is an important step to clarify the gene expression profile during preeclampsia genesis and development stage.更多还原