Long-term excessive intake of fluoride (F) can cause osseous and non-osseous damage. The kidney is the main fluoride excretion organ of the body. This study aimed to explore whether dietary calcium (Ca) supplementation can alleviate kidney damage caused by fluorosis and to further investigate the effects of Ca on the mitigation mechanism of renal cell apoptosis triggered by F. We evaluated the histopathological structure, renal function indicators, and gene and protein expression levels of death receptor-mediated apoptosis pathways in Sprague Dawley (SD) rats treated with sodium fluoride (NaF) and/or calcium carbonate (CaCO₃) for 120 days. The results showed that 100 mg/L NaF induced kidney histopathological injury and apoptosis, increased the concentrations of Creatinine (CRE), uric acid (UA), blood urea nitrogen (BUN), potassium (K), phosphorus (P) and F (p < 0.05), and decrease the level of serum magnesium (Mg) (p < 0.05). Moreover, NaF increased the mRNA and protein expression levels of Fas cell surface death receptor (FAS), tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand (TRAIL), Caspase 8, Caspase 3 and poly ADP-ribose polymerase (PARP) (p < 0.01), which finally activated the death receptor pathway. Inversely, Ca supplementation reversed the decrease of CRE, BUN, UA, F and P levels induced by F, alleviated histopathological damage and apoptosis, and reduced the gene and protein expression levels of death receptor pathway-related markers. In conclusion, 1% Ca alleviates F-induced kidney apoptosis through FAS/FASL, TNFR/TNF, DR5/TRAIL signaling pathways.

长期过量摄入氟化物（F）可引起骨性和非骨性损伤。肾脏是人体主要的氟排泄器官。本研究旨在探讨膳食钙（Ca）补充是否可以减轻氟中毒引起的肾损伤，并进一步研究钙对氟中毒引起的肾细胞凋亡的缓解机制的影响。我们评估了组织病理学结构、肾功能指标和用氟化钠 (NaF) 和/或碳酸钙 (CaCO ₃) 120 天。结果表明，100 mg/L NaF可诱导肾脏组织病理学损伤和细胞凋亡，增加肌酐（CRE）、尿酸（UA）、血尿素氮（BUN）、钾（K）、磷（P）和F的浓度（p  < 0.05)，并降低血清镁 (Mg) 水平（p  < 0.05）。此外，NaF 增加了 Fas 细胞表面死亡受体 (FAS)、肿瘤坏死因子 (TNF)、TNF 相关凋亡诱导配体 (TRAIL)、Caspase 8、Caspase 3 和聚 ADP-核糖聚合酶的 mRNA 和蛋白质表达水平。 PARP) ( p < 0.01)，最终激活死亡受体通路。相反，Ca 补充逆转了 F 诱导的 CRE、BUN、UA、F 和 P 水平的降低，减轻了组织病理学损伤和细胞凋亡，并降低了死亡受体通路相关标志物的基因和蛋白质表达水平。总之，1% Ca 通过 FAS/FASL、TNFR/TNF、DR5/TRAIL 信号通路减轻 F 诱导的肾细胞凋亡。