基于代谢组学的子宫内膜异位症发病机制和诊断生物标志物研究

项目名称： 基于代谢组学的子宫内膜异位症发病机制和诊断生物标志物研究

项目编号： No.81460232

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杨必成

作者单位： 江西省妇幼保健院

项目金额： 48万元

中文摘要： 子宫内膜异位症（EMs）中存在大量差异表达的异常基因和蛋白，这些差异表达的异常基因和蛋白必然会引起其下游产物也是最终产物即小分子代谢产物的变化，因此我们前期采用高分辨质谱测定了EMs患者和正常对照者血清中的代谢产物，发现EMs患者确实存在大量差异代谢产物，因此进行基于代谢组学的EMs研究,可能会为进一步阐述EMs的发病机制和生物标志物奠定基础。为此，拟建立基于MS的代谢组学方法，绘制EMs患者血清、尿液和组织的代谢图谱，进行统计学分析，找到相关差异代谢产物及其代谢通路。分离培养子宫内膜间质细胞，通过RNA干扰手段改变代谢通路相关基因观察其对子宫内膜间质细胞生物学功能的影响，对代谢组学结果进行体外验证。将相关代谢通路改变的转基因子宫内膜间质细胞及母本细胞接种至人工控制生理周期的裸鼠背部皮下，动态观察接种细胞的生长、增殖、凋亡与浸润以及微血管密度等情况，以对代谢组学结果进行体内验证。

中文关键词： 子宫内膜异位症；代谢组学；发病机制；生物标志物

英文摘要： The pathogenesis and mechanism of endometriosis still remains unclear. Results of many studies suggest the existence of many differentially expressed genes and proteins involved in endometriosis. Metabolites are the end products of cellular regulatory processes, and their levels can be regarded as the ultimate response of biological systems to genetic or proteinic changes. In our previous research, serum metabolic profiling employing time-of-flight mass spectrometry (TOFMS) was utilized to investigate the complex physiopathologic regulations in endometriosis. It was revealed that metabolic differences between endometriosis patients and healthy controls could be observed, so it will be informative to investigate the potential machanisms and biomarkers of endometriosis by metabolomics. In the current study, different conditions for metabolomics analysis will be performed and optimized on TOFMS, and we will make metabolomic research on serum, urine and endometrium samples from endometriosis patients and healthy controls. The different metabolite and related metabolic pathway will be identified. In order to validate the results of metabolomic on endometriosis, we will isolate and culture stromal cells from endometria of EMs patients and control patients without EMs, and evaluate their proliferation, apoptosis, adhesion, invasion in vitro. In addition, these functions will be examined after RNA interference used to silence related metabolic genes. Finally, transgenic stromal cells and maternal stromal cells will be implanted in female nude mice, and evaluate proliferative activity, VEGF expression, apoptosis and invasion, this vivo models of endometriosis will be used for further validate the results of metabolomics.

英文关键词： endometriosis;metabolomics;machanisms;biomarkers