Mesoporous silica nanoparticles (MSNs) are widely used in many biomedical applications and clinical fields. However, the applications of MSNs are limited by their severe toxicity. Apigenin (AG) has demonstrated pharmacological effects with low toxicity. The aim of this study was to clarify the role of AG in the progression of MSNs-induced renal injury. BALB/c mice and NRK-52E cells were exposed to MSNs with or without AG. AG protected mice and NRK-52E cells from the MSNs-induced pathological variations in renal tissues and decreased cell viability. AG significantly reduced the levels of serum blood urea nitrogen (BUN) and serum creatinine (Scr), upregulated the levels of superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT), and improved the pathological changes of the kidney in MSNs-treated mice. The protective effects of AG were associated with its ability to increase the levels of antioxidants, reduce the accumulation of ROS, and inhibit the expression of the inflammatory mediators (TNF-α, IL-6). In addition, AG treatment upregulated the activity of FOXO3a, increased the level of IkBα, and reduced the nuclear translocation of NF-κB, which ultimately alleviated MSNs-induced inflammation. Nuclear FOXO3a translocation also triggered antioxidant gene transcription and protected nephrocyte from oxidative damage. However, knockdown of FOXO3a significantly blocked the protective effects of AG. These findings suggested that AG could be a promising therapeutic strategy for MSNs-induced nephrotoxicity, and this protective effect might be related to the suppression of oxidative stress and inflammation via the FOXO3a/NF-κB pathway.

介孔二氧化硅纳米粒子 (MSN) 广泛用于许多生物医学应用和临床领域。然而，MSN 的应用受到其严重毒性的限制。芹菜素 (AG) 具有低毒性的药理作用。本研究的目的是阐明 AG 在 MSNs 诱导的肾损伤进展中的作用。BALB/c 小鼠和 NRK-52E 细胞暴露于有或没有 AG 的 MSN。AG 保护小鼠和 NRK-52E 细胞免受 MSNs 诱导的肾组织病理变化和细胞活力降低。AG显着降低血清尿素氮（BUN）和血清肌酐（Scr）水平，上调超氧化物歧化酶（SOD）、谷胱甘肽（GSH）和过氧化氢酶（CAT）水平，改善MSNs肾脏病理改变处理过的小鼠。AG的保护作用与其增加抗氧化剂水平、减少ROS积累和抑制炎症介质（TNF-α、IL-6）表达的能力有关。此外，AG 治疗上调了 FOXO3a 的活性，增加了 IkBα 的水平，并减少了 NF-κB 的核转位，最终缓解了 MSNs 诱导的炎症。核 FOXO3a 易位还触发了抗氧化基因转录并保护肾细胞免受氧化损伤。然而，FOXO3a 的敲低显着阻断了 AG 的保护作用。这些发现表明，AG 可能是一种有前景的 MSNs 诱导的肾毒性治疗策略，这种保护作用可能与通过 FOXO3a/NF-κB 通路抑制氧化应激和炎症有关。