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全氟辛酸(PFOA)暴露通过过度激活雄性小鼠中的巨噬细胞诱导脾脏萎缩。

Perfluorooctanoic acid (PFOA) exposure induces splenic atrophy via overactivation of macrophages in male mice.

机构信息

Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

J Hazard Mater. 2021 Apr 5;407:124862. doi: 10.1016/j.jhazmat.2020.124862. Epub 2020 Dec 15.

DOI:10.1016/j.jhazmat.2020.124862
PMID:33360190
Abstract

Perfluorooctanoic acid (PFOA), a synthetic and widely used chemical, has aroused wide public concern due to its persistence, bioaccumulation, and potential toxicity. To investigate splenic atrophy induced by PFOA, male mice were exposed to 0, 0.4, 2, or 10 mg/kg/d PFOA for 28 d. Results demonstrated that spleen weight and relative spleen weight (RSW) decreased in the 2 and 10 mg/kg/d PFOA exposure groups. Iron levels in the spleen and serum were also reduced in all PFOA exposure groups. Weighted gene co-expression network analysis (WGCNA) of 7 043 genes highlighted enrichment in cell cycle, autoimmunity, and anemia in the spleen. In addition, changes in the levels of hemoglobin, platelets, bilirubin, and heme oxygenase-1 were consistent with anemia. The ratio of total macrophages to M1 macrophages in the spleen, phagocytic ability of macrophages, and levels of cytokines such as TNF-α, IL-1β, and IL-6 all increased, thus suggesting the occurrence of autoimmune disorder. Therefore, we concluded that overactivation of macrophages may be an important reason for splenic atrophy induced by PFOA exposure.

摘要

全氟辛酸(PFOA)是一种合成的、广泛使用的化学物质,由于其持久性、生物蓄积性和潜在毒性,引起了公众的广泛关注。为了研究 PFOA 引起的脾脏萎缩,雄性小鼠暴露于 0、0.4、2 或 10 mg/kg/d PFOA 28 天。结果表明,2 和 10 mg/kg/d PFOA 暴露组的脾脏重量和相对脾脏重量(RSW)降低。所有 PFOA 暴露组的脾脏和血清中的铁水平也降低。对 7043 个基因的加权基因共表达网络分析(WGCNA)突出了脾脏中细胞周期、自身免疫和贫血的富集。此外,血红蛋白、血小板、胆红素和血红素加氧酶-1 水平的变化与贫血一致。脾脏中总巨噬细胞与 M1 巨噬细胞的比例、巨噬细胞的吞噬能力以及 TNF-α、IL-1β 和 IL-6 等细胞因子的水平均升高,提示自身免疫紊乱的发生。因此,我们得出结论,巨噬细胞的过度激活可能是 PFOA 暴露引起脾脏萎缩的一个重要原因。

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