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体内慢性铅毒性的剂量依赖性效应:关注微量元素和肠道微生物群。

Dose-dependent effects of chronic lead toxicity in vivo: Focusing on trace elements and gut microbiota.

机构信息

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, 214122, China.

出版信息

Chemosphere. 2022 Aug;301:134670. doi: 10.1016/j.chemosphere.2022.134670. Epub 2022 Apr 19.

DOI:10.1016/j.chemosphere.2022.134670
PMID:35452643
Abstract

Dose-dependent effects of chronic Pb exposure-induced injuries, especially on the trace elements and gut microbiota in mice, have not been explored. In the present study, we investigated these aspects using C57BL/6 mouse models that were exposed to Pb via drinking water with Pb concentrations of 0.1, 0.5, and 1.0 g/L for 8 weeks. The results showed that with the increase in chronic Pb exposure dose, the Pb levels in the blood and tissues, Zn levels in the kidney and brain were elevated, and the levels of bone Zn, kidney Fe, brain Mg, Ca, and Fe, renal catalase activity, and glutathione levels, as well as the expression of colonic zonula occludens-1 and occludin, decreased with a strong linear correlation. Moreover, the relative abundance of Marvinbryantia and Ruminococcus 1 increased, while that of Lactobacillus and Roseburia decreased linearly with the Pb exposure dose. PICRUSt analysis revealed that chronic Pb exposure had a greater impact on the metabolism of macronutrients, trace elements, and neurodegenerative injury. These findings suggest that chronic Pb exposure disrupts trace element levels in tissues, especially in the brain, and induces gut dysbiosis in a dose-dependent manner, which is different from the dose-effect of acute Pb toxicity.

摘要

慢性 Pb 暴露诱导损伤的剂量依赖性效应,特别是对小鼠的微量元素和肠道微生物群,尚未得到探索。在本研究中,我们使用 C57BL/6 小鼠模型通过饮用水暴露于 0.1、0.5 和 1.0 g/L Pb 8 周来研究这些方面。结果表明,随着慢性 Pb 暴露剂量的增加,血液和组织中的 Pb 水平、肾脏和大脑中的 Zn 水平升高,而骨骼 Zn、肾脏 Fe、大脑 Mg、Ca 和 Fe 水平、肾过氧化氢酶活性和谷胱甘肽水平以及结肠紧密连接蛋白-1 和闭合蛋白的表达降低,呈强线性相关。此外,Marvinbryantia 和 Ruminococcus 1 的相对丰度线性增加,而 Lactobacillus 和 Roseburia 的相对丰度则随 Pb 暴露剂量线性减少。PICRUSt 分析表明,慢性 Pb 暴露对宏量营养素、微量元素和神经退行性损伤的代谢有更大的影响。这些发现表明,慢性 Pb 暴露会破坏组织中的微量元素水平,特别是大脑中的微量元素水平,并以剂量依赖性方式引起肠道菌群失调,这与急性 Pb 毒性的剂量效应不同。

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