uNK细胞杀伤受体及其配体与URSA母胎免疫紊乱分子机制研究

项目名称： uNK细胞杀伤受体及其配体与URSA母胎免疫紊乱分子机制研究

项目编号： No.81501336

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王红丹

作者单位： 郑州大学

项目金额： 18万元

中文摘要： 原因不明复发性流产 (URSA) 是妇产科常见的并发症，病因复杂。为了探讨妊娠后胚胎和母体相互作用机制，阐明部分URSA发病机理，本课题拟先研究URSA患者和正常孕妇子宫蜕膜NK (uNK) 细胞亚型比例和毒性变化规律，在细胞水平探讨uNK细胞在URSA发生中的作用；在基因、蛋白和mRNA水平上，通过检测两组子宫蜕膜KIRs、绒毛HLA-C、-G和HLA-E，探索其分布规律及KIR/HLA配对规律，进一步探讨uNK细胞在URSA发生中的作用；在此基础上，对目标KIR和HLA基因可能结合的miRNA进行预测，对两组子宫蜕膜和绒毛组织目标miRNA进行检测，筛选出差异表达miRNA，进行mRNA-miRNA整合分析；通过以上研究明确uNK在URSA发生中的分子作用机制。本课题更全面更深入的对uNK细胞在URSA发生中作用进行了研究，为以后进一步的研究URSA发生机制及进行个体化治疗奠定基础。

中文关键词： 原因不明复发性流产；自然杀伤细胞；杀伤细胞免疫球蛋白样受体；人类白细胞抗原

英文摘要： Unexplained recurrent spontaneous abortion is a common complication of obstetrics and gynecology, the reasons of which are complex. To investigate the interaction mechanism between the embryo and the matrix after pregnancy, and clarify the pathogenesis of some unexplained recurrent miscarriage, this research project is to first study the subtype proportion and change rule of toxicity of the uNK cell of URSA patients and normal controls pregnant, exploring the role that uNK cells play during the occurring of URSA at a cellular level; and through the detection of the two groups of the KIRs in suterine decidua, HLA-C, -G and HLA-E in villi tissue, it is to explore their distribution and KIR/HLA matching rule at gene, protein and mRNA level, and further explore the role that uNK cells play during the occurring of URSA. On this basis, this research is to predict the miRNA which may be target of KIR and HLA genes, to detect the target miRNA of the two groups of uterine decidua and villi tissue, screening differentially expressed miRNA, and to make mRNA - miRNA integration analysis. Through the above research, it aims to make clear the molecular mechanism of uNK during the occurring of URSA. This topic makes more comprehensive and in-depth studies to the roles that uNK cells play during the occurring of URSA, which lays a foundation for further studying URSA occurrence mechanism and individualized treatment.

英文关键词： unexplained recurrent spontaneous abortion;natural killer cell;killer cell immunoglobulin-like receptors;human leucocyte antigen