miR-21通过调节NF-κB信号途径对感染性早产发病机制的影响

Infectious preterm birth (IPTB) is the main factors resulted in the higher morbidity and mortality of perinatal infant, which its mechanism has not been fully elucidated. MiR-21 was the key component of the NF-κB regulation network, which played an important role in NF-κB-mediated inflammatory pathway. Our preliminary experiments showed that miR-21 overexpression downregulated NF-κB protein, and inhibition of miR-21 upregulated NF-κB protein. Hereby, we speculated that miR-21 may be involved in onset process of IPTB by adjusting NF-κB pathway. In this study, chorioamnionitis was as a center-link of IPTB, miR-21 and NF-κB was as the key breakthrough point in the inflammation regulation network, glucocorticoid hormone drugs-dexamethasone (DXM) was for the intervention measures. We further explore whether miR-21 was involved in IPTB by NF-κB signaling pathways, and influence of DXM on miR-21expression. This study will help to formulate the strategies of treatment and prevention for IPTB, and provide new direction for research and development of new miRNAs-target drug.

感染性早产（Infectious preterm birth，IPTB）是导致围生儿发病率和死亡率升高的最主要因素，其机制尚未完全阐明。miR-21在NF-κB 介导的炎症通路中发挥着重要调节功能，是NF-κB调控网络中的关键成分。我们前期实验发现：miR-21过表达下调NF-κB蛋白表达，而抑制miR -21则上调NF-κB蛋白表达；故推测miR-21可能通过调节NF-κB通路参与IPTB发病过程。故本课题针对IPTB发病的中心环节——绒毛膜羊膜炎，以炎症调控网络中的关键成分miR-21和NF-κB为切入点，以糖皮质激素类药物地塞米松（dexamethasone，DXM）为干预措施，从整体、细胞、分子水平三个层次探讨miR-21通过NF-κB信号途径在IPTB中的作用以及DXM对miR-21的影响，将有助于制定IPTB的治疗和预防策略，研发新型药物的靶标提供新的方向。

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，以炎症调控网络中的关键成分miR-21和NF-κB为切入点，以经典的糖皮质激素类药物DXM为干预措施。采用RT-PCR, western-bloting，细胞转染，激光共聚焦等技术通过观察胎盘绒毛膜组织和滋养层细胞miR-21的表达及DXM干预作用。结果阐明：（1）miR-21通过调节NF-κB信号通路参与IPTB的发病机制；（2）DXM能够剂量依赖性的促进miR-21的表达，miR-21有可能是DXM治疗IPTB新的作用靶点；（3）miR-21 mimics替代治疗可改善绒毛膜羊膜炎，该研究有助于研发以miR-21为靶标治疗IPTB的新药提供方向。