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高温与臭氧共同暴露诱导小鼠心血管损伤:来自肠道微生物组和血浆代谢组学的见解

High temperature and ozone co-exposure induces cardiovascular damage in mice: Insights from gut microbiome and plasma metabolomics.

作者信息

Wu Qiong, Xu Fei, Yang Yishu, Zhang Aogang, Sun Han, Yang Lin, Zhao Shuaiqi, Zeng Yuling, Wang Mengxin, Shi Saige, Zhang Fengquan, An Zhen, Li Juan, Li Huijun, Wu Hui, Zhuo Laibao, Song Jie, Chen Wen, Wu Weidong

机构信息

Henan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China.

Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.

出版信息

Ecotoxicol Environ Saf. 2025 Jul 1;299:118323. doi: 10.1016/j.ecoenv.2025.118323. Epub 2025 May 19.

DOI:10.1016/j.ecoenv.2025.118323
PMID:40393318
Abstract

Epidemiological studies have demonstrated associations between heat waves, ozone (O) pollution, and cardiovascular morbidity and mortality. High temperature (HT) and higher levels of O usually co-exist in the atmosphere. However, few studies have investigated the adverse effects of HT and O co-exposure on cardiovascular system. Therefore, this study aimed to examine the effects of HT and O co-exposure on biomarkers of cardiovascular damage and potential mechanisms. Sixty-four healthy SPF male C57BL/6N mice, aged 8 weeks, were randomly allocated into four groups: control, O, HT, and co-exposure (HT+O). Mice inhaled filtered air or 1 ppm O at 24 °C or 36 °C, respectively, 4 h/day, for 5 consecutive days. Following the exposure, the biological samples of mice were collected for examination of biomarkers of cardiovascular disorders. Exposure to HT+O exacerbated cardiovascular pathological damage induced by HT or O alone. Compared to the control, the co-exposure group caused significant alterations of cardiovascular biomarkers. Moreover, co-exposure enhanced reduction of Lactobacillus and Ruminococcus and increases in Prevotella and Alistipe abundances induced by either HT or O. Moreover, co-exposure also promoted O-induced plasma metabolic disorder and these metabolites were enriched in multiple metabolic pathways typified by steroid hormone biosynthesis, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism, among others. Spearman correlation analysis indicated that alterations of gut microbiota were significantly correlated with biomarkers of cardiovascular damage as well as plasma metabolic disorder. Exposure to HT and O leads to cardiovascular damage, which possibly implicates gut microbial dysbiosis and plasma metabolic disorder.

摘要

流行病学研究表明,热浪、臭氧(O₃)污染与心血管疾病的发病率和死亡率之间存在关联。高温(HT)和较高水平的O₃通常在大气中同时存在。然而,很少有研究调查HT和O₃共同暴露对心血管系统的不良影响。因此,本研究旨在探讨HT和O₃共同暴露对心血管损伤生物标志物及潜在机制的影响。将64只8周龄的健康SPF级雄性C57BL/6N小鼠随机分为四组:对照组、O₃组、HT组和共同暴露组(HT+O₃)。小鼠分别在24℃或36℃下吸入过滤空气或1 ppm O₃,每天4小时,连续5天。暴露后,收集小鼠的生物样本,检测心血管疾病生物标志物。HT+O₃共同暴露加剧了单独HT或O₃诱导的心血管病理损伤。与对照组相比,共同暴露组引起心血管生物标志物的显著改变。此外,共同暴露增强了HT或O₃单独诱导的乳酸杆菌和瘤胃球菌的减少以及普雷沃氏菌和阿利斯蒂普菌丰度的增加。此外,共同暴露还促进了O₃诱导的血浆代谢紊乱,这些代谢产物在以类固醇激素生物合成、不饱和脂肪酸生物合成和苯丙氨酸代谢等为代表的多个代谢途径中富集。Spearman相关性分析表明,肠道微生物群的改变与心血管损伤生物标志物以及血浆代谢紊乱显著相关。HT和O₃暴露导致心血管损伤,这可能与肠道微生物群失调和血浆代谢紊乱有关。

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