LAMA4甲基化异常参与调控子痫前期发病的机制研究

Preeclampsia is a kind of pregnancy -specific disease which is characterized by high blood pressure and proteinuria It is a serious threat to maternal and child health . Because of its complex pathogenesis , prevention and treatment strategies currently are not ideal , make it a hot topic in obstetrics . Epigenetic research,in particular DNA methylation is an important factor in preeclampsia . Our subject was found that expression of LAMA4 in early chorionic villi,normal term pregnancy and preeclampsia placenta respectively was decreased ; while in different trophoblast cell lines, methylation status and expression of LAMA4 were changed by oxidative stress and methylation inhibitor (5-aza-CdR)meanwhile, suggesting that LAMA4 DNA methylation may affect trophoblasts biological function especially invasion ability . This study aims to utilize technology of cell biology and epigenetics, combines with tissue testing, cell lines and primary cells ( trophoblast cells and endothelial cells ) in vitro culture, explores oxidative stress - methylation regulation - trophoblastic dysfunction, revealing LAMA4 DNA methylation modification was anomalies in the pathogenesis of preeclampsia. This study will provide new ideas for the prevention and treatment of pre-eclampsia.

子痫前期是以高血压、蛋白尿为主要特征的妊娠期特有的疾病，严重威胁母婴健康。因其发病机制复杂，目前尚无理想的防治策略，多年来一直是产科的研究热点。表观遗传学特别是DNA甲基化是子痫前期发病的重要因素。本课题前期发现LAMA4在早孕绒毛、正常晚孕及子痫前期胎盘中表达逐渐降低；同时，在不同侵袭能力的滋养细胞株中，LAMA4受氧化应激及甲基化抑制剂（5-aza-CdR）的影响，甲基化状态发生改变的同时伴表达差异，提示LAMA4 DNA甲基化对滋养细胞生物功能尤其是侵袭能力的影响。本课题旨在通过细胞生物学及表观遗传学技术，结合组织检测、体外原代细胞及细胞株（滋养细胞及内皮细胞）培养，通路验证，探究氧化应激-甲基化调控-滋养细胞功能障碍这一设想，揭示LAMA4 DNA甲基化修饰异常在子痫前期发病机制中的作用，为子痫前期的预防及诊治提供新的思路。