hsa_circRNA_0007478/miR-765调控巨噬细胞焦亡介导动脉粥样硬化炎症反应的作用研究

巨噬细胞焦亡及慢性炎症是动脉粥样硬化发生发展的关键因素。circRNAs表达不当导致疾病发生。我们前期研究发现：在ox-LDL刺激的巨噬细胞中，细胞焦亡增加，hsa_circRNA_0007478表达和NLRP3、IL-1β水平上调，miR-765表达下调，而采用miR-765过表达或siRNA沉默circRNA_0007478基因可同向缓解这些炎症反应；且证实circRNA_0007478与miR-765存在碱基互补配对，可靶向调控。基于此，我们提出1）circRNA_0007478作为miR-765的天然海绵，靶向吸附miR-765调控巨噬细胞焦亡介导炎症反应；2）hsa_circRNA_0007478可能成为动脉粥样硬化防治的新靶点。因此，本研究欲利用ox-LDL刺激的巨噬细胞和ApoE-/-小鼠模型，采用分子生物学实验，阐明上述假设，为动脉粥样硬化的防治提供新的分子依据和治疗靶点。

Pyroptosis in macrophages and chronic inflammation are key factors in the pathological process of atherosclerosis. And unbalanced expression of circRNAs lead to diseases development. Our previous study showed that hsa_circRNA_0007478（circRNA_0007478）expression, NLRP3 and IL-1β level upregulated, miR-765 decreased and pyroptosis increased in macrophages by oxLDL. Moreover, down-regulation of circRNA_0007478 or up-regulation of miR-765 can abolish inflammation in oxLDL-induced macrophages. Besides, it exists complementary base pairing between circRNA_0007478 and miR-765 sequences. Based on these results, we propose that 1) circRNA_0007478, as a natural sponge for miR-765, targets miR-765 to regulate macrophage pyroptosis and mediate inflammation; 2) hsa_circRNA_0007478 may be a new target for the prevention and treatment of atherosclerosis. Thus, we will establish atherosclerosis model in vivo and in vitro, including ox-LDL-stimulated macrophages and ApoE-/-mouse models, to verify the above assumptions, and provide a new therapeutic target for the prevention and treatment of atherosclerosis.