Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China.
Environ Toxicol. 2024 Nov;39(11):5086-5098. doi: 10.1002/tox.24387. Epub 2024 Aug 1.
The health risks associated with microplastics have attracted widespread attention. Polystyrene microplastics (PS-MPs) can induce damage to cardiac tissue, while pyroptosis-mediated injury to the vascular endothelial plays a vital role in the pathogenesis of cardiovascular diseases. The study intended to explore the role and mechanism of NLR family pyrin domain containing 3 (NLRP3) mediated pyroptosis in PS-MPs causing the injury of vascular endothelial cells. In vivo, Wistar rats were exposed to 0.5, 5, and 50 mg/kg/d 0.5 μm PS-MPs. In vitro, the human vascular endothelial cells (HUVECs) were used for mechanistic studies. siRNA was used for silencing the NILRP3 gene. H&E staining and flow cytometry were performed to examine the vascular injury and cell membrane damage. The oxidative stress was detected by flow cytometry, immunofluorescence, and corresponding kits. ELISA were used to measure the levels of inflammatory factors. Real-time PCR and western blot were used to measure the expression of pyroptosis signaling pathway. In rats, PS-MPs could cause vascular damage, oxidative stress, and inflammatory response, and activated the pyroptosis signaling pathway. HUVECs exposure to PS-MPs, the vitality decreased in a dose-dependent manner, ROS and MDA were significantly increased while SOD was decreased. PS-MPs induced the onset of pyroptosis signaling pathway in HUVECs. Cell membrane damage and the levels of IL-Iβ and IL-18 in HUVECs significantly increased, those are symbols for the development of pyroptosis. Inhibition of NLRP3-mediated pyroptosis effectively protected HUVECs from PS-MPs-induced damage. Pyroptosis played a vital role in controlling the vascular endothelial injury caused by PS-MPs.
与微塑料相关的健康风险引起了广泛关注。聚苯乙烯微塑料（PS-MPs）可诱导心肌组织损伤，而细胞焦亡介导的血管内皮损伤在心血管疾病的发病机制中起着至关重要的作用。本研究旨在探讨 NOD、LRR 和富含亮氨酸重复蛋白 3（NLRP3）介导的细胞焦亡在 PS-MPs 导致血管内皮细胞损伤中的作用和机制。在体内，Wistar 大鼠暴露于 0.5、5 和 50mg/kg/d 的 0.5μm PS-MPs 中。在体外，使用人血管内皮细胞（HUVEC）进行机制研究。使用 siRNA 沉默 NLRP3 基因。使用 H&E 染色和流式细胞术检测血管损伤和细胞膜损伤。通过流式细胞术、免疫荧光和相应试剂盒检测氧化应激。ELISA 用于测量炎症因子水平。实时 PCR 和 Western blot 用于测量细胞焦亡信号通路的表达。在大鼠中，PS-MPs 可引起血管损伤、氧化应激和炎症反应，并激活细胞焦亡信号通路。HUVEC 暴露于 PS-MPs 后，细胞活力呈剂量依赖性下降，ROS 和 MDA 明显增加，SOD 降低。PS-MPs 诱导 HUVEC 中细胞焦亡信号通路的发生。HUVEC 细胞膜损伤和 IL-Iβ 和 IL-18 水平显著增加，这是细胞焦亡发展的标志。抑制 NLRP3 介导的细胞焦亡可有效保护 HUVEC 免受 PS-MPs 诱导的损伤。细胞焦亡在控制 PS-MPs 引起的血管内皮损伤中起着至关重要的作用。
