脓毒症严重心肌炎症致心肌损伤并加重脓毒症损害。细胞焦亡介导多种心脏病，但其在脓毒症心肌损伤中的作用未明。我们前期RNA-seq测序发现环状RNA circAbl1在脓毒症小鼠心肌中下调，过表达circAbl1减轻心肌细胞炎症和焦亡。此外，circAbl1可吸附miR-22-3p，上调miR-22-3p靶基因caveolin-3（Cav-3），减少焦亡。RNA沉淀发现circAbl1亦可直接结合Cav-3。我们推测脓毒症心肌circAbl1通过miR-22-3p和/或直接调控Cav-3，减少心肌炎症和焦亡，减轻心肌损伤。我们拟建立circAbl1基因敲除小鼠在体和离体脓毒症模型，结合circAbl1、miR-22-3p、和Cav-3腺病毒转染或基因沉默，探讨circAbl1通过miR-22-3p依赖和非依赖途径调控Cav-3对脓毒症心肌细胞焦亡和心肌损伤的影响。为脓毒症心肌损伤防治提供依据。

Sepsis is aggravated by sever myocardial inflammation that leads to cardiac injury. Programmed cell death has been suggested to be the main cause of this process. Pyroptosis, a newly identified type of programmed cell death that mainly triggered by inflammation, plays important roles in cardiac diseases, however, its role in sepsis-induced cardiac injury is unclear. Using RNA-seq, we have identified a circRNA, circAbl1, that is downregulated in cardiac tissue from mice with sepsis. Overexpression of circAbl1 reduced inflammatory cytokines release and decreased cardiomyocytes (CMs) pyroptosis in lipopolysaccharides (LPS)-challenged CMs. Further, we found that circAbl1 can bind to microRNA-22-3p (miR-22-3p), thereby increased cavoline-3 (a direct downstream target of miR-22-3p) and decreased CMs pyroptosis in LPS-challenged CMs. Moreover, RNA pulldown of circAbl1 showed that circAbl1 can directly bind to caveolin-3. These above preliminary findings prompted us to postulate that in hearts from sepsis, overexpression of circAbl1 regulates caveolin-3 by working as a sponge that binds to miR-22-3p or by directly binding, which results in reduction of inflammation and pyroptosis, and eventually attenuate cardiac injury in sepsis. We will conduct series experiments using in vivo animal and in vitro cell models of sepsis in normal and circAbl1 knockout mice, incorporating the use of cicrAbl1, miR-22-3p, and caveolin-3 adenoviruses or siRNAs to address mechanisms. This study will provide new insights regarding the molecular mechanism whereby circAbl1/miR-22-3p/caveolin-3 in sepsis-induced cardiac injury and its interplay with pyroptosis. This study will facilitate the development of effective therapy to combat sepsis-induced cardiac injury.