妊娠期糖尿病（GDM）是最常见的孕期并发症之一，GDM患者发生早产、巨大儿、产后糖尿病和心血管疾病的风险明显增高。近年研究发现细胞分泌的外泌体能够携带特殊的miRNA作用于靶器官并与代谢疾病的发病有关，但GDM的具体发生机制尚不清楚。课题组前期利用芯片筛查提示正常妊娠的胎盘与GDM的胎盘组织中miRNA表达有差异；二代测序发现两者胎盘来源的外泌体miRNA也存在差异，信息分析显示高表达的miR-577的靶基因是FGF21，其与肝细胞糖脂代谢调节有关，而FGF21的下游信号通路是PI3K/Akt。本研究将通过不同的肝细胞和小鼠模型，采用细胞功能实验、GDM小鼠功能回复等多种分子生物学实验方法，从分子、细胞、组织、动物水平来阐明胎盘源性外泌体携带miR-577靶向FGF21及下游PI3K/Akt通路调控肝细胞胰岛素抵抗在GDM发病中的作用及机制，为GDM的临床诊治提供实验基础和理论依据。

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. Patients with GDM have a significantly increased risk of premature delivery, giant fetus, postpartum diabetes and cardiovascular disease. Recent studies have found that exosomes secreted by cells can carry special miRNA to target organs and are related to the occurrence of metabolic diseases. However, the mechanism on GDM is still unclear. In our early study, microarray screening indicated that miRNA expression from placenta tissue was different between the normal pregnancy and the GDM pregnancy. The next generation sequencing revealed that there were also differences in exosome miRNA from placenta cells between the two groups. Information analysis showed that the target gene of specific miR-577 was FGF21, which involving the regulation of glucose and fat metabolism in liver cells, and the downstream signal pathway of FGF21 was PI3K/Akt. In this research, we will illustrate the pathogenesis mechanism of GDM involving that the exosomes secreted by placenta cells can carry miR-577, which targets FGF21 and PI3K/Akt pathway, to regulate the insulin resistance in liver cells from the level of molecules, cells, tissues and animals, the study will be performed through different liver cells and mouse models, using various experimental methods of molecular biology, such as cell function test and functional recovery of GDM mice. In order to provide experimental basis and theoretical foundation for clinical diagnosis and treatment of GDM.