lncRNA MALAT1/miR-124/STAT3轴调节慢乙肝患者肝脏炎症的作用及其机制研究

The mechanism of hepatic Kupffer cells which negatively feedback regulate liver inflammation in hronic hepatitis B (CHB) and HBV relatated ACLF patients remains largely unknow. In previous study we found that serum miR-124 levels is correlated with liver injury in CHB and HBV-ACLF patients. miR-124 may directly inhibit the activation of IL-6 on STAT3 via targeting STAT3. In addition, miR-124 may be combined with lncRNA MALAT1, blocking the activation of pro-inflammatory pathway and macrophage polarization. We hypothesized that the MALAT1/miR-124/STAT3 axis may regulate macrophage polarization and thus play a protective role in the regulation of liver inflammation in CHB patients. Based on previous studies, we plan to verify the interaction of MALAT1 and miR-124 in vitro. Furthermore, we will investigate the regulation of MALAT1/miR-124/STAT3 axis on liver inflammation and the potential therapeutic effect of miR-124 in mouse models. This study is helpful to elucidate the mechanism of negative feedback regulation of Kupffer cells in acute exacerbation of liver inflammation, and to provide a theoretical basis for the treatment of severe liver inflammation.

肝内巨噬细胞（Kupffer）负反馈调节慢乙肝患者急性加重的肝脏炎症机制尚未阐明。我们在前期研究中发现，miR-124与慢乙肝及HBV-ACLF患者肝脏炎症损伤程度相关，可能通过靶作用于STAT3，直接抑制IL-6对STAT3的活化；另外，miR-124可能通过与lncRNA MALAT1结合，阻断促炎通路的激活及M1型巨噬细胞极化。我们推测，可能存在MALAT1/miR-124/STAT3轴调节巨噬细胞极化，从而对慢乙肝患者肝脏炎症发挥一种保护性的反馈调节作用。我们拟在前期研究的基础上，通过体外实验验证MALAT1与miR-124的相互作用；在小鼠模型中，验证MALAT1/miR-124/STAT3轴对肝脏炎症的调控以及miR-124潜在的治疗作用。本研究有助于阐明在急性加重的肝脏炎症中Kupffer细胞的负反馈调节机制，为阻断细胞因子风暴导致严重的肝脏炎症的治疗新策略提供理论依据。

肝内巨噬细胞(Kupffer)负反馈调节慢乙肝患者急性加重的肝脏炎症机制尚未阐明。我 们在前期研究中发现，miR-124与慢乙肝及HBV-ACLF患者肝脏炎症损伤程度相关，可能通过靶作用于STAT3，直接抑制IL-6对STAT3的活化;另外，miR-124可能通过与lncRNA MALAT1结合， 阻断促炎通路的激活及M1型巨噬细胞极化。我们推测，可能存在MALAT1/miR-124/STAT3轴调节 巨噬细胞极化，从而对慢乙肝患者肝脏炎症发挥一种保护性的反馈调节作用。我们拟在前期研究的基础上，通过体外实验验证MALAT1与miR-124的相互作用;在小鼠模型中，验证MALAT1/miR-124/STAT3轴对肝脏炎症的调控以及miR-124潜在的治疗作用。本研究助于阐明在急性加重的肝脏炎症中Kupffer细胞的负反馈调节机制，为阻断细胞因子风暴导致严重的肝脏炎症的治疗新策略提供理论依据。