Sun Yan, Zhang Lu, Liu Jinguo, Zhang Xiaoping, Su Yan, Yin Quanling, He Shuangxi
College of Basic Medical Sciences , Shenyang Medical College , Shenyang 110034 , China . Email:
Lunar and Planetary Science Laboratory , MUST-Partner Laboratory of Key Laboratory of Lunar and Deep Space Exploration , CAS , China.
Toxicol Res (Camb). 2019 May 6;8(4):499-508. doi: 10.1039/c8tx00329g. eCollection 2019 Jul 1.
The objective of this study was to investigate the effects of lunar dust simulant (LDS) on cardiac function and fibrosis. In an experiment, after 3 weeks of exposure, electrocardiography (ECG) and histopathological and immunohistochemical analyses of the cardiac tissue were performed. Systemic inflammatory markers and genes and proteins associated with cardiac tissue fibrosis were examined. In an experiment, fibrosis-related factors were detected in H9c2 cells by western blot and the mechanism of myocardial fibrosis by LDS exposure was explored. LDS exposure significantly altered heart rate indicators, implying altered cardiac and autonomic system functions. LDS dose-dependently increased the type and number of ECG abnormalities, and increased serum inflammatory factors. In addition, pathological changes in the myocardial tissue were observed through hematoxylin and eosin, Masson, and immunohistochemical staining; the expression of genes and proteins related to fibrosis in the myocardial tissue was also altered. These findings indicate that LDS exposure causes systemic inflammatory lesions that affect autonomic function, leading to inflammatory myocardial fibrosis. And its mechanisms involve the mediation of the nuclear factor-E2-related factor (Nrf2)/nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) redox balance.
本研究的目的是调查月球尘埃模拟物(LDS)对心脏功能和纤维化的影响。在一项实验中,暴露3周后,对心脏组织进行了心电图(ECG)、组织病理学和免疫组织化学分析。检测了全身炎症标志物以及与心脏组织纤维化相关的基因和蛋白质。在另一项实验中,通过蛋白质免疫印迹法在H9c2细胞中检测纤维化相关因子,并探讨LDS暴露导致心肌纤维化的机制。LDS暴露显著改变了心率指标,这意味着心脏和自主神经系统功能发生了改变。LDS剂量依赖性地增加了心电图异常的类型和数量,并增加了血清炎症因子。此外,通过苏木精-伊红染色、Masson染色和免疫组织化学染色观察到心肌组织的病理变化;心肌组织中与纤维化相关的基因和蛋白质表达也发生了改变。这些发现表明,LDS暴露会导致全身性炎症病变,影响自主神经功能,进而导致炎症性心肌纤维化。其机制涉及核因子E2相关因子(Nrf2)/烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(NOX4)氧化还原平衡的介导作用。