Song Chenchen, Zhou Li, Xiong Yi, Zhao Lianlian, Guo Jindan, Zhang Ling, Han Yunlin, Yang Hu, Xu Yanfeng, Zhao Wenjie, Shan Shan, Sun Xiuping, Zhang Boxiang, Guo Jianguo
State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Sciences, CAMS&PUMC, Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Beijing 100021, China.
Department of Food Science and Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China.
Ecotoxicol Environ Saf. 2025 Apr 1;294:118065. doi: 10.1016/j.ecoenv.2025.118065. Epub 2025 Mar 26.
PM, recognized as a potential pathogenic factor for nervous system diseases, remains an area with many unknowns, particularly regarding its effects on human health. After five-month real-ambient PM exposure, we observed no significant pathological damage to the lung, liver, spleen, or kidney tissues. However, PM exposure led to neuronal degeneration in the hippocampal CA1 region of Brown Norway (BN) rats. The level of IL-6, IL-13, IL-1β, IL-12, IL-4, GRO/KC, MIP-1α, CM-CSF significantly increased in lung lavage fluid (P < 0.05 for all). Notably, we detected a slight impairment in spatial learning ability, as evidenced by the Barnes maze training outcomes. There were no significant changes in the bacterial community in lung lavage fluid (P = 0.621), but the bacterial community in the gut significantly changed (P < 0.001), with more species identified (P < 0.05). The metabolomic analysis revealed 147 and 149 significantly changed metabolites in the pulmonary system and serum, respectively (P < 0.05). PM exposure caused a decrease in Nervonic acid (NA) in both the lung and serum, which likely contributed to spatial learning impairment (P < 0.01). The correlation between lung metabolites, gut bacterial species, and serum metabolites indicated that PM exposure likely impaired spatial learning through the lung-gut-brain axis pathway. Lung and serum metabolic disorders and intestinal microbial imbalance occurred in BN rats post-five-month real-ambient PM exposure. There were two potential ways that PM exposure caused the decline of spatial learning ability in wild-type BN rats: (1) PM exposure led to a significant decrease of neuroprotective Nervonic acid in lung and serum metabolites. (2) PM exposure likely led to reduced spatial learning ability through the lung-gut-brain axis.
颗粒物（PM）被认为是神经系统疾病的一个潜在致病因素，但仍存在许多未知领域，尤其是其对人类健康的影响。在进行了五个月的实际环境PM暴露实验后，我们观察到肺、肝、脾或肾组织没有明显的病理损伤。然而，PM暴露导致了棕色挪威（BN）大鼠海马CA1区的神经元退化。肺灌洗液中白细胞介素-6（IL-6）、白细胞介素-13（IL-13）、白细胞介素-1β（IL-1β）、白细胞介素-12（IL-12）、白细胞介素-4（IL-4）、生长调节致癌基因蛋白/角质形成细胞趋化因子（GRO/KC）、巨噬细胞炎性蛋白-1α（MIP-1α）、粒-巨噬细胞集落刺激因子（CM-CSF）的水平显著升高（所有P值均<0.05）。值得注意的是，通过巴恩斯迷宫训练结果证明，我们检测到空间学习能力略有受损。肺灌洗液中的细菌群落没有显著变化（P = 0.621），但肠道中的细菌群落发生了显著变化（P < 0.001），鉴定出的物种更多（P < 0.05）。代谢组学分析显示，肺系统和血清中分别有147种和149种代谢物发生了显著变化（P < 0.05）。PM暴露导致肺和血清中的神经酸（NA）减少，这可能导致了空间学习障碍（P < 0.01）。肺代谢物、肠道细菌种类和血清代谢物之间的相关性表明，PM暴露可能通过肺-肠-脑轴途径损害空间学习能力。在五个月的实际环境PM暴露后，BN大鼠出现了肺和血清代谢紊乱以及肠道微生物失衡。PM暴露导致野生型BN大鼠空间学习能力下降有两种潜在方式：（1）PM暴露导致肺和血清代谢物中具有神经保护作用的神经酸显著减少。（2）PM暴露可能通过肺-肠-脑轴导致空间学习能力下降。
