TCDD慢性暴露与母体免疫功能在腭裂发生中的交互作用及其分子机制研究

项目名称： TCDD慢性暴露与母体免疫功能在腭裂发生中的交互作用及其分子机制研究

项目编号： No.81500830

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： 杨运强

作者单位： 华中科技大学

项目金额： 17万元

中文摘要： 唇腭裂的发病机制较为复杂，除环境等因素外，有学者发现对于实验动物模型给予免疫刺激可明显降低腭裂的发生，因此唇腭裂的发生还与母体的免疫作用相关。目前对于母体免疫功能与环境因素在腭裂发生中的交互作用机制尚不明确，更缺乏模拟实际发病过程的环境因素慢性暴露的动物模型。二恶英（TCDD）在众多可疑影响唇腭裂发生的环境因素中最为明确、致畸性最强。本项目通过前期建立的TCDD慢性暴露诱导的小鼠腭裂模型，拟在TCDD慢性暴露和TCDD慢性暴露+免疫刺激剂作用于C57BL/6J小鼠的两种环境情况下，应用激光显微切割技术、荧光定量PCR等技术，按时空顺序研究腭胚突融合阶段关键基因信号通路的变化规律，并观察免疫刺激剂（GM-CSF, IFNγ）对母体免疫功能和腭胚突发育的影响与干预机制。阐明二恶英慢性暴露与母体免疫功能交互作用对腭胚突融合影响的机制，探索不利环境情况下对腭裂高危人群干预性预防的新途径。

中文关键词： 腭裂；二恶英；慢性暴露；中嵴上皮细胞；信号通路

英文摘要： The pathogenesis of cleft lip and palate is relatively complex, in addition to environmental and other factors, some scholars found that the experimental animal model for immune stimulation can obviously reduce the occurrence of cleft palate, therefore, the occurrence of cleft lip and palate is also associated with the maternal immune function. For the interaction mechanism between maternal immune function and environmental factors in the formation of cleft palate is unclear, a lack of chronic exposure animal model simulating the actual incidence of environmental factors presently.Dioxin (TCDD) in many dubious environmental factors in the formation of cleft lip and palate is the most clear, the strongest teratogenicity.So we plan to apply Laser Micro-Dissection and Real-time RT-PCR and other technology to study the spatiotemporal expression pattern of the key gene signal pathway in the fusion process of embryonic palate in the two statement of “chronic TCDD exposure ”and “chronic TCDD exposure+ immunologic stimulant” effcting C57BL/6J mice based on the former established chroni TCDD exposure-induced cleft palate mice in this project ,and we would also observe the influence of immunologic stimulant（GM-CSF, IFNγ）on maternal immunity and the development of embryonic palate andresearch its interventional mechanism at the same time. By this way we want to illuminate how the interaction between chronic TCDD exposure and maternal immunity would influence the fusion of embryonic palate, and find a new way of preventive intervention on high risk groups of cleft palate under unfavourable environment.

英文关键词： cleft palate;2;3;7;8-tetrachloro-dibenzo-p-dioxin;chronic exposure;medial edge epithelial cell;signal pathway