大气颗粒物与心血管疾病密切相关。纳米SiO2是大气颗粒物惰性核之一，课题组前期发现其损伤心肌线粒体，抑制SIRT3活性，导致心肌收缩力减弱、心率降低。本研究拟采用Wistar大鼠和人诱导性多能干细胞（hIPSCs）分化的心肌细胞研究纳米SiO2颗粒在心律失常发生发展中的作用及机理。体内实验建立纳米SiO2低剂量染毒大鼠模型，检测心脏结构、功能、心电图、氧化应激、线粒体膜电位、能量代谢、ATP、NAD+/NADH、SIRT3、CaMKⅡ、钙和钙通道蛋白，从“线粒体SIRT3-ROS-CaMKⅡ-钙超载-电生理传导异常”角度探讨纳米SiO2致心律失常作用。机制研究采用抗氧化剂N-乙酰半胱氨酸、SIRT3过表达和CaMKⅡ特异抑制剂KN-93，利用hIPSCs分化的心肌细胞，验证SIRT3/ROS/CaMKⅡ在纳米SiO2致心律失常中的调控作用，为心血管疾病早期防治和大气颗粒物标准制订提供依据。

Atmospheric particulate matter is closely related to cardiovascular disease. Silica nanoparticle is one of the inert nuclei of atmospheric particulate matter. Our previous research found that silica nanoparticles did damage on the mitochondria of myocardium, inhibited the activity of SIRT3, reduced myocardial contractility and heart rate. In this study, Wistar rats and myocardial cells differentiated from human induced pluripotent stem cells, hIPSCs, were used to investigate the effects of silica nanoparticles on the occurrence and development of arrhythmia, and its related mechanisms. The in vivo rat model with low-dose silica nanoparticles exposure was performed, and the cardiac structure, function, electrocardiogram, oxidative stress, mitochondrial membrane potential, energy metabolism, ATP content, NAD+/NADH ratio, SIRT3, CaMK II, calcium content and calcium channel proteins were all determined to explore the induction of arrhythmia by silica nanoparticles from the perspective of "mitochondrial SIRT3-ROS-CaMKⅡ-calcium overload-electrophysiological conduction abnormality". In the mechanism study, the hIPSCs-differentiated myocardial cells as cell model, and the antioxidant N-acetylcysteine, SIRT3 over-expression and CaMK II-specific inhibitor, KN-93, were used to validate the regulatory role of SIRT3-ROS-CaMKⅡ in cardiac arrhythmias induced by silica nanoparticles. The research would provide evidence for early prevention and control of cardiovascular disease and the development of standards for atmospheric particulate matter.