Abstract：
Fluorosis due to high fluoride levels in drinking water profoundly affects the development of human skeletal and dental structures. Sodium butyrate (NaB) has been found to regulate overall bone mass and prevent pathological bone loss. However, the mechanism of NaB action on fluorosis remains unclear. In this study, a rat model of fluorosis induced by 100 mg/L sodium fluoride was used to investigate the impact of NaB on bone homeostasis and serum metabolomics. It was found that NaB significantly reduced the levels of bone resorption markers CTX-Ⅰ and TRACP-5B in fluorosis rats. Moreover, NaB increased calcium and magnesium levels in bone, while decreasing phosphorus levels. In addition, NaB improved various bone microstructure parameters, including bone mineral density (BMD), trabecular thickness (Tb. Th), trabecular bone separation (Tb. SP), and structural model index (SMI) in the femur. Notably, NaB intervention also enhanced the antioxidant capacity of plasma in fluorosis rats. Furthermore, a comprehensive analysis of serum metabolomics by LC-MS revealed a significant reversal trend of seven biomarkers after the intervention of NaB. Finally, pathway enrichment analysis based on differential metabolites indicated that NaB exerted protective effects on fluorosis by modulating arginine and proline metabolic pathways. These findings suggest that NaB has a beneficial effect on fluorosis and can regulate bone homeostasis by ameliorating metabolic disorders.
摘要：
由于饮用水中的高氟化物水平而导致的氟中毒会严重影响人体骨骼和牙齿结构的发育。已发现丁酸钠（NaB）可调节整体骨量并防止病理性骨丢失。然而,NaB对氟中毒的作用机制尚不清楚.在这项研究中,使用100mg/L氟化钠诱导的氟中毒大鼠模型，研究NaB对骨稳态和血清代谢组学的影响。结果发现NaB能显著降低氟中毒大鼠骨吸收标志物CTX-Ⅰ和TRACP-5B的水平。此外，NaB增加了骨骼中的钙和镁水平，同时降低磷水平。此外,NaB改善各种骨微结构参数，包括骨矿物质密度（BMD），小梁厚度(Tb.Th),骨小梁分离（Tb。SP),和股骨结构模型指数(SMI)。值得注意的是,NaB干预还增强了氟中毒大鼠血浆的抗氧化能力。此外，通过LC-MS对血清代谢组学进行的综合分析显示,NaB干预后7种生物标志物有显著逆转趋势.最后,基于差异代谢产物的途径富集分析表明，NaB通过调节精氨酸和脯氨酸代谢途径对氟中毒具有保护作用。这些发现表明，NaB对氟中毒具有有益作用，并可以通过改善代谢紊乱来调节骨稳态。
