申请人前期发现，CVB3感染的雌雄小鼠心脏浸润巨噬细胞lncRNA表达谱存在显著差异。通过生物信息学分析及lncRNA靶基因反向预测，结合体外功能实验，发现AK085865差异最为明显，且高表达于M2型巨噬细胞，敲减AK085865可抑制BMDMs向M2极化，提示AK085865参与了巨噬细胞极化，然而其机制不明。本研究中，我们拟通过阻断或过表达等方法，探讨AK085865在巨噬细胞极化中的调控作用；通过RNA pulldown及质谱分析鉴定AK085865结合蛋白，进而深入研究AK085865与结合蛋白的表达调控关系及AK085865-蛋白质复合体调控巨噬细胞极化的下游分子机制；通过构建基因敲除小鼠模型，观察AK085865对病毒性心肌炎发病的影响，试图阐明AK085865调控巨噬细胞极化在病毒性心肌炎中的作用及其分子机制，从而为病毒性心肌炎发病机制研究和生物治疗提供新的理论和实验依据。

Viral myocarditis (VM) is a kind of clinical common infectious disease of cardiovascular system. Accumulating documents indicated that cardiac injury was associated with heart-infiltrating macrophages and differentially polarizated macrophages played a role in VM. However, mechanisms that underlie macrophage polarization remain largely undefined. Our preliminary experiments found that differentially expressed lncRNA profiles existed in in heart infiltrated macrophages from CVB3 infected male and female mice, indicating that individual lncRNA may play a role in macrophage polarization. By the advanced bioinformatics analysis and reverse prediction of lncRNA target gene, combined with in vitro functional experiments, we found that AK085865 expression difference was most obvious, and high expression in M2 macrophages. AK085865 Knockdown could inhibit BMDMs to M2 polarization, suggesting that AK085865 is involved in the macrophage polarization process, but its mechanism is largely unknown..In the present study, we aim to explore the role of AK085865 in the regulation of macrophage polarization by gain or loss of functions. Meanwhile, we will identify protein targets binding to AK085865 by RNA pull-down and mass spectrometry analysis and explore the molecular mechanism of lncRNA-protein complex in regulating macrophage polarization. Besides, we will explore the possible mechanisms of AK085865 in regulating macrophage polarization and its potential role in VM by constructing a knockout mouse model. Our study will help to further understand the mechanism of VM and provide a novel therapeutic strategy in treating inflammatory cardiac disease.