Department of Environmental Health, School of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China.
Int J Mol Sci. 2022 Jul 27;23(15):8266. doi: 10.3390/ijms23158266.
Fluoride is widely distributed, and excessive intake will lead to dental fluorosis. In this study, six offspring rats administrated 100 mg/L sodium fluoride were defined as the dental fluorosis group, and eight offspring rats who received pure water were defined as the control group. Differentially expressed proteins and metabolites extracted from peripheral blood were identified using the liquid chromatography tandem mass spectrometry and gas chromatography mass spectrometry, with the judgment criteria of fold change >1.2 or <0.83 and p < 0.05. A coexpression enrichment analysis using OmicsBean was conducted on the identified proteins and metabolites, and a false discovery rate (FDR) < 0.05 was considered significant. Human Protein Atlas was used to determine the subcellular distribution of hub proteins. The Gene Cards was used to verify results. A total of 123 up-regulated and 46 down-regulated proteins, and 12 up-regulated and 2 down-regulated metabolites were identified. The significant coexpression pathways were the HIF-1 (FDR = 1.86 × 10−3) and glycolysis/gluconeogenesis (FDR = 1.14 × 10−10). The results of validation analysis showed the proteins related to fluorine were mainly enriched in the cytoplasm and extrinsic component of the cytoplasmic side of the plasma membrane. The HIF-1 pathway (FDR = 1.01 × 10−7) was also identified. Therefore, the HIF-1 and glycolysis/gluconeogenesis pathways were significantly correlated with dental fluorosis.
氟广泛分布，摄入过量会导致氟斑牙。本研究中，给予 100mg/L 氟化钠的 6 只仔鼠被定义为氟斑牙组，给予纯水的 8 只仔鼠被定义为对照组。采用液相色谱串联质谱和气相色谱质谱联用技术鉴定外周血中差异表达的蛋白质和代谢物，判断标准为 fold change>1.2 或 <0.83，p<0.05。对鉴定的蛋白质和代谢物进行 OmicsBean 共表达富集分析，以 FDR<0.05 为显著差异。利用人类蛋白质图谱确定关键蛋白的亚细胞分布，利用基因卡片对结果进行验证。共鉴定到 123 个上调蛋白和 46 个下调蛋白，12 个上调代谢物和 2 个下调代谢物。显著共表达通路为 HIF-1（FDR=1.86×10−3）和糖酵解/糖异生（FDR=1.14×10−10）。验证分析结果表明，与氟相关的蛋白主要富集在细胞质和质膜细胞质外侧的外在成分中。还鉴定到 HIF-1 通路（FDR=1.01×10−7）。因此，HIF-1 和糖酵解/糖异生通路与氟斑牙显著相关。
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