Abstract：
Carbon black nanoparticles (CBNPs) are widely distributed in the environment and are increasingly recognized as a contributor in the development of cardiovascular disease. A variety of cardiac injuries and diseases result from structural and functional damage to cardiomyocytes. This study explored the mechanisms of CBNPs-mediated myocardial toxicity. CBNPs were given to mice through intra-tracheal instillation and it was demonstrated that the particles can be taken up into the cardiac tissue. Exposure to CBNPs induced cardiomyocyte inflammation and apoptosis. In combination with in vitro experiments, we showed that CBNPs increased the ROS and induced mitochondria fragmentation. Functionally, CBNPs-exposed cardiomyocyte exhibited depolarization of the mitochondrial membrane potential, release of cytochrome c, and activation of pro-apoptotic BAX, thereby initiating programmed cell death. On the other hand, CBNPs impaired autophagy, leading to the inadequate removal of dysfunctional mitochondria. The excess accumulation of damaged mitochondria further stimulated NF-κB activation and triggered the NLRP3 inflammasome pathway. Both the antioxidant N-acetylcysteine and the autophagy activator rapamycin were effective to attenuate the damage of CBNPs on cardiomyocytes. Taken together, this study elucidated the potential mechanism underlying CBNPs-induced myocardial injury and provided a scientific reference for the evaluation and prevention of the CBNPs-related heart risk.
摘要：
炭黑纳米颗粒(CBNPs)在环境中广泛分布,并且越来越被认为是心血管疾病发展的贡献者。多种心脏损伤和疾病是由心肌细胞的结构和功能损伤引起的。本研究探讨了CBNPs介导的心肌毒性的机制。通过气管内滴注将CBNP给予小鼠，并证明了颗粒可以吸收到心脏组织中。暴露于CBNPs诱导心肌细胞炎症和凋亡。结合体外实验，我们表明CBNP增加了ROS并诱导了线粒体片段化。功能上,CBNP暴露的心肌细胞表现出线粒体膜电位的去极化，细胞色素c的释放，和促凋亡BAX的激活，从而引发程序性细胞死亡。另一方面,CBNPs受损的自噬，导致功能失调的线粒体去除不足。受损线粒体的过度积累进一步刺激NF-κB激活并触发NLRP3炎性体途径。抗氧化剂N-乙酰半胱氨酸和自噬激活剂雷帕霉素均可有效减轻CBNPs对心肌细胞的损伤。一起来看,本研究阐明了CBNPs致心肌损伤的潜在机制,为CBNPs相关心脏风险的评估和预防提供了科学依据。
