CircRNA_0002873-miR-21-TLR4途径在感染性早产中的作用及调控机制

The pathogenesis of infectious preterm (IPTB) has not been fully elucidated. Chorioamnionitis (CAs) was a pathological feature of IPTB. miR-21 and TLR4 were closely related to IPTB. CircRNA was as a new RNA molecules with regulation of miRNA function, widely involved in the disease process of many diseases. Our preliminary circRNA-Seq experiments showed that the increase of circRNA_0002873 expression and the decrease of miR-21 in placenta tissues with IPTB. miR-21 overexpression decreased MyD88 and TRAF6 protein of TLR4 downstream signals. Hereby, we speculated that circRNA_0002873 may be involved in the CAs by downregulating miR-21. In this study, CAs was as a center-link of IPTB, circRNA_0002873 was as a research targets, miR-21and TLR4 was as the key breakthrough point. FISH，cell transfection, luciferase reporter gene assays, and siRNA were used, respectively. This study will further elucidate the pathogenesis of circRNA_0002873-miR-21-TLR4 pathway in the IPTB，and help to provide theoretical basis for the prevention and treatment of IPTB for the future research and development for circRNA-targets drugs.

感染性早产（IPTB）的发病机制未完全阐明。绒毛膜羊膜炎（CAs）是IPTB的病理基础。miR-21和TLR4信号途径与IPTB密切相关。circRNA为一种新的调控miRNA功能的RNA分子，广泛参与了多种疾病的发病过程。我们前期研究发现：胎盘组织中circRNA_0002873的表达升高，miR-21表达降低；miR-21过表达能下调TLR4下游MyD88和TRAF6蛋白表达，故推测circRNA_0002873可能通过下调miR-21参与IPTB的发病机制。因此，本课题针对IPTB发病的中心环节——CAs，以circRNA_0002873为研究靶点，以miR-21和TLR4为切入点，采用FISH、细胞转染、荧光素酶报告基因检测、siRNA等，阐明circRNA_0002873-miR-21-TLR4途径在IPTB的调控机制，为将来研发以circRNA为靶点的药物提供理论依据。

感染性早产（IPTB）是导致围生儿发病率和死亡率升高的最主要因素。本课题采用LPS诱导感染性早产模型和滋养层细胞模型，针对IPTB发病的中心环节——绒毛膜羊膜炎，以circRNA_0002873为研究靶点，以炎症调控网络中的关键成分miR-21和TLR4为切入点。采用circRNA基因测序、荧光原位杂交（FISH）、siRNA、细胞转染、荧光素酶报告基因检测、RT-PCR、Western-Blot及激光共聚焦等技术，从整体、细胞、分子水平三个层次的结果阐明：（1）circRNA_0002873通过调节miR-21-TLR4的表达参与感染性早产（IPTB）的发病机制；（2）circRNA_0002873能成为治疗IPTB新的作用靶点之一，该研究有助于研发以circRNA_0002873为靶标治疗IPTB的新药提供理论依据。