Department of Environmental Health, School of Public Health and the Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.
Shanghai Key Laboratory of Meteorology and Health, Shanghai, China.
Ecotoxicol Environ Saf. 2019 Jun 15;174:92-99. doi: 10.1016/j.ecoenv.2019.02.064. Epub 2019 Feb 26.
Epidemiological evidences have indicated that fine particulate matter (PM) is associated with the increased risk of cardiovascular morbidity and mortality. Although several mechanisms linking PM and inflammatory responses have been widely implicated, the detailed mechanisms involving the occurrence of inflammation in PM-induced adverse effects are lacking. This study aims to investigate whether PM exposure-induced cardiovascular injury is associated with NLRP3 inflammasome activation in apolipoprotein E (Apo E) mice. Thirty-two Apo E mice were randomly divided into four groups. The mice were fed with normal chow (NC) or high-fat chow (HFC) for 10 weeks, respectively. From week 11, the mice were exposed to concentrated PM (PM) or filter air (FA) using Shanghai Meteorological and Environmental Animal Exposure System for 16 weeks. The cardiac function and myocardial injury were evaluated by echocardiography and histopathological examination. Meanwhile, the expression of NLRP3-related signaling pathway in myocardium was detected. Compared with the FA mice, the PM mice showed the underlying cardiac dysfunction and injury in both NC and HFC groups. Mononuclear macrophages (CD11c) were significant higher in bone marrow of the PM mice than that in the FA mice, whilst CD206 macrophages were lower. Accordingly, PM exposure induced the increase of circulating inflammatory cytokine TNF-α and decrease of anti-inflammatory cytokine IL-10. PM exposure was also associated with the activation of NLRP3 inflammasome, which characterized by elevated protein expression of NLRP3, ASC, caspase-1, IL-1β and IL-18 in myocardium. All these results demonstrated PM-related cardiac injury is mediated by macrophages polarization and NLRP3 inflammasome activation.
流行病学证据表明，细颗粒物（PM）与心血管发病率和死亡率的增加有关。虽然已经广泛涉及将 PM 与炎症反应联系起来的几种机制，但涉及 PM 诱导的炎症发生的详细机制尚不清楚。本研究旨在探讨 PM 暴露诱导的心血管损伤是否与载脂蛋白 E（ApoE）小鼠中 NLRP3 炎性体激活有关。32 只 ApoE 小鼠被随机分为四组。分别用普通饲料（NC）或高脂饲料（HFC）喂养 10 周。从第 11 周开始，使用上海气象环境动物暴露系统将小鼠暴露于浓缩 PM（PM）或过滤空气（FA）中 16 周。通过超声心动图和组织病理学检查评估心脏功能和心肌损伤。同时，检测心肌中 NLRP3 相关信号通路的表达。与 FA 组相比，PM 组在 NC 和 HFC 组均表现出潜在的心脏功能障碍和损伤。单核巨噬细胞（CD11c）在 PM 组骨髓中的表达明显高于 FA 组，而 CD206 巨噬细胞则较低。相应地，PM 暴露诱导循环炎症细胞因子 TNF-α的增加和抗炎细胞因子 IL-10 的减少。PM 暴露还与 NLRP3 炎性体的激活有关，其特征在于心肌中 NLRP3、ASC、caspase-1、IL-1β和 IL-18 的蛋白表达增加。所有这些结果表明，PM 相关的心脏损伤是由巨噬细胞极化和 NLRP3 炎性体激活介导的。
