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暴露于多壁碳纳米管(MWCNTs)和邻苯二甲酸二丁酯(DBP)的组合会导致小鼠脾脏毒性。

Exposure to a combination of MWCNTs and DBP causes splenic toxicity in mice.

作者信息

Zhou Tingting, He Yueyan, Qin Yujie, Wang Bing, Zhang Hongmao, Ding Shumao

机构信息

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, Hubei, China.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, Hubei, China.

出版信息

Toxicology. 2022 Jan 15;465:153057. doi: 10.1016/j.tox.2021.153057. Epub 2021 Dec 3.

Abstract

The large conjugated π bond in the molecular structure of carbon nanotubes (CNTs) interacts with the benzene ring structure in di (n-butyl) phthalates (DBP) through a π - π bond. Compounds of CNTs and DBP form easily, becoming another environmental pollutant of concern. We explore whether CNTs entering animals slow down the degradation of the DBP adsorbed in the CNT cavity, thereby prolonging the "hormonal activity" of DBP. In our study, male BALb/c mice were used as experimental subjects divided into four groups: the control group; the multi-walled carbon nanotubes (MWCNTs) exposure group (10mg/kg/d); the DBP exposure group (2.15 mg/kg/d); and the compound exposure group (MWCNTs + DBP). After 30 days of exposure, the mice were sacrificed and their spleens used for immunotoxicology study. The results showed that the exposure groups exhibited splenomegaly and suffered severe oxidative damage to the spleen. In the compound exposure group: levels of IgA and IgG in the serum of the mice changed, and were significantly different from levels in both the MWCNTs and DBP exposure groups (p <0.05); the pathological sections of the spleen showed that the boundary between the white pulp area (WP) and the red pulp area (RP) was blurred, that the cell arrangement was loose, and that more red blood cells were retained in the spleen. Proteomics mass spectrometry analysis showed that compared with the control group, 70 proteins were up-regulated and 27 proteins were down-regulated in the MWCNTs group, 36 proteins were up-regulated and 23 proteins were down-regulated in the DBP group, 87 proteins were up-regulated and 21 proteins were down-regulated in the compound exposure group. The results of GO enrichment analysis and KEGG enrichment analysis of the differentially expressed proteins showed that the compound exposure harmed the spleen antigen recognition, processing, and presentation, inhibited the activation and proliferation of B cells and T cells, and hindered the adaptive immune responses. Our results showed that MWCNTs and DBP compounds can damage the spleen, and impair the innate and adaptive immune functions of the body.

摘要

碳纳米管(CNTs)分子结构中的大共轭π键通过π-π键与邻苯二甲酸二(正丁基)酯(DBP)中的苯环结构相互作用。碳纳米管与DBP的化合物易于形成,成为另一种令人担忧的环境污染物。我们探究进入动物体内的碳纳米管是否会减缓吸附在碳纳米管腔内的DBP的降解,从而延长DBP的“激素活性”。在我们的研究中,将雄性BALb/c小鼠作为实验对象,分为四组:对照组;多壁碳纳米管(MWCNTs)暴露组(10mg/kg/d);DBP暴露组(2.15mg/kg/d);以及复合暴露组(MWCNTs + DBP)。暴露30天后,处死小鼠并取其脾脏用于免疫毒理学研究。结果表明,各暴露组均出现脾肿大,脾脏遭受严重氧化损伤。在复合暴露组中:小鼠血清中IgA和IgG水平发生变化,且与MWCNTs和DBP暴露组水平均有显著差异(p<0.05);脾脏病理切片显示,白髓区(WP)和红髓区(RP)之间的边界模糊,细胞排列疏松,脾脏中滞留了更多红细胞。蛋白质组学质谱分析表明,与对照组相比,MWCNTs组中有70种蛋白质上调,27种蛋白质下调;DBP组中有36种蛋白质上调,23种蛋白质下调;复合暴露组中有87种蛋白质上调,21种蛋白质下调。对差异表达蛋白质的GO富集分析和KEGG富集分析结果表明,复合暴露损害了脾脏的抗原识别、加工和呈递,抑制了B细胞和T细胞的激活和增殖,阻碍了适应性免疫反应。我们的结果表明,MWCNTs与DBP的化合物会损害脾脏,削弱机体的固有免疫和适应性免疫功能。

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