线粒体动力学障碍是对乙酰氨基酚（APAP）肝损伤的关键机制。我们研究首次发现：APAP肝损伤中p66Shc表达显著增加，敲减p66Shc明显改善APAP肝损伤线粒体动力学。进一步发现：抑制线粒体内膜蛋白酶OMA1泛素化是p66Shc引起APAP肝损伤线粒体动力学障碍的重要途径；生物信息学预测和预实验提示circ-CBFB可通过海绵效应调控p66Shc的表达。据此提出科学假说：p66Shc抑制OMA1泛素化调节线粒体动力学在APAP肝损伤中发挥重要作用，通过circ-CBFB的海绵效应调控p66Shc/OMA1信号轴减轻APAP肝损伤。本研究利用基因模式动物及分子生物学技术，探讨circ-CBFB调控p66Shc/OMA1信号轴影响线粒体动力学在APAP肝损伤中的作用及机制，为APAP肝损伤治疗提供新的策略及药物研发靶标。

Mitochondrial dynamics imbalance is the key mechanism of acetaminophen (APAP)-induced liver injury. Our preliminary studies found that in APAP-induced liver injury p66Shc expression is significantly increased, and knock-down of p66Shc obviously alleviates mitochondrial dynamics imbalance of APAP-induced liver injury. We further found that inhibition of mitochondrial inner membrane protease (OMA1) ubiquitination is an important pathway of mitochondrial dynamics imbalance induced by p66Shc in APAP-induced liver injury. Bioinformatics and pre-experiment indicated that circ-CBFB can regulate p66Shc expression through sponge effect. Therefore, we hypothesize that p66Shc, which regulates mitochondrial dynamics by inhibiting OMA1 ubiquitination, plays a vital role in APAP-induced liver injury. Modulation of p66Shc/OMA1 axis by circ-CBFB through sponge effect can alleviate mitochondrial dynamics imbalance in APAP-induced liver injury. In this study, by utilizing genetic animal model and molecular biological techniques, we investigate the role and mechanism of circ-CBFB-p66Shc/OMA1 signaling in APAP-induced liver injury and intend to provide a novel therapeutic strategy and a pharmacological target for the treatment of APAP-induced liver injury.