细颗粒物 (PM 2.5 ) 暴露与心血管疾病 (CVD) 的发病率和死亡率有关。线粒体是PM 2.5的敏感靶点，线粒体功能障碍与CVD的发生密切相关。PM 2.5引发心肌细胞线粒体损伤的表观遗传机制尚不清楚。本研究聚焦miR-421/SIRT3信号通路，探讨PM 2.5诱导大鼠H9c2细胞心脏线粒体动力学失衡的调控机制。结果表明，PM 2.5会损害线粒体功能并导致动态稳态失衡。此外，PM 2.5上调 miR-421 和下调 SIRT3 基因表达，同时降低 p-FOXO3a（SIRT3 下游靶基因）和 p-Parkin 表达并引发融合基因 OPA1 和裂变基因 Drp1 的异常表达。此外，miR-421 抑制剂 (miR-421i) 和白藜芦醇显着提高暴露于 PM 2.5后 H9c2 细胞中的 SIRT3 水平，并介导 SOD2、OPA1 和 Drp1 的表达，恢复线粒体形态和功能。这表明 miR-421/SIRT3 通路在 PM 2.5诱导的线粒体损伤中发挥表观遗传调节作用，并且 miR-421i 和白藜芦醇对 PM 2.5引起的心脏毒性发挥保护作用。

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Fine particulate matter (PM2.5) exposure is associated with cardiovascular disease (CVD) morbidity and mortality. Mitochondria are sensitive targets of PM2.5, and mitochondrial dysfunction is closely related to the occurrence of CVD. The epigenetic mechanism of PM2.5-triggered mitochondrial injury of cardiomyocytes is unclear. This study focused on the miR-421/SIRT3 signaling pathway to investigate the regulatory mechanism in cardiac mitochondrial dynamics imbalance in rat H9c2 cells induced by PM2.5. Results illustrated that PM2.5 impaired mitochondrial function and caused dynamics homeostasis imbalance. Besides, PM2.5 up-regulated miR-421 and down-regulated SIRT3 gene expression, along with decreasing p-FOXO3a (SIRT3 downstream target gene) and p-Parkin expression and triggering abnormal expression of fusion gene OPA1 and fission gene Drp1. Further, miR-421 inhibitor (miR-421i) and resveratrol significantly elevated the SIRT3 levels in H9c2 cells after PM2.5 exposure and mediated the expression of SOD2, OPA1 and Drp1, restoring the mitochondrial morphology and function. It suggests that miR-421/SIRT3 pathway plays an epigenetic regulatory role in mitochondrial damage induced by PM2.5 and that miR-421i and resveratrol exert protective effects against PM2.5-incurred cardiotoxicity.