Zhang Wenxiao, Qi Di, Pei Xiaoting, Lu Dingli, Ba Mengru, Xuan Shuting, Huang Duliurui, Yang Tingting, Yang Jingwen, Li Zhijie, Huang Shenzhen
Department of Ophthalmology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
Henan Key Laboratory of Ophthalmology and Visual Science, Henan Eye Hospital and Henan Eye Institute, People's Hospital of Henan University, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
J Nanobiotechnology. 2025 Sep 2;23(1):600. doi: 10.1186/s12951-025-03630-5.
Sleep deprivation (SD) and exposure to engineered nanomaterials such as silica nanoparticles (SiNPs) are emerging risk factors for ocular surface disorders, particularly dry eye disease. However, the molecular mechanisms underlying their combined impact on lacrimal gland function remain unclear. In this study, we investigated the synergistic effects of SD and SiNPs exposure on circadian regulation, oxidative stress, inflammation, and structural integrity of the extraorbital lacrimal glands (ELGs) in C57BL/6J mice. Behavioral and physiological monitoring revealed that SD + SiNPs disrupted circadian locomotor activity and body temperature rhythms. Phenotypic assessments showed reduced tear secretion and ELG atrophy. RNA sequencing identified extensive transcriptomic reprogramming, including altered expression of core clock genes and enrichment of inflammatory and redox-related pathways. Increased reactive oxygen species (ROS) accumulation and γ-H2AX expression indicated oxidative DNA damage. Immunohistochemistry confirmed NLRP3 inflammasome activation, while Western blotting revealed enhanced phosphorylation of JAK2, STAT3, NF-κB p65, and IκBα, alongside upregulation of IL-17A. Elevated malondialdehyde levels further reflected oxidative lipid damage. These findings demonstrate that SD exacerbates SiNPs-induced ELG dysfunction via circadian disruption and activation of the ROS/NLRP3/IL-17A inflammatory axis. While these effects are currently limited to the lacrimal gland, future studies are needed to determine whether similar mechanisms contribute to broader systemic metabolic consequences.
睡眠剥夺（SD）以及接触工程纳米材料如二氧化硅纳米颗粒（SiNPs）正成为眼表疾病的新兴风险因素，尤其是干眼病。然而，它们对泪腺功能的联合影响的分子机制仍不清楚。在本研究中，我们调查了SD和暴露于SiNPs对C57BL/6J小鼠眶外泪腺（ELGs）昼夜节律调节、氧化应激、炎症和结构完整性的协同作用。行为和生理监测显示，SD + SiNPs破坏了昼夜运动活动和体温节律。表型评估显示泪液分泌减少和ELG萎缩。RNA测序确定了广泛的转录组重编程，包括核心时钟基因表达的改变以及炎症和氧化还原相关途径的富集。活性氧（ROS）积累增加和γ-H2AX表达表明氧化性DNA损伤。免疫组织化学证实了NLRP3炎性小体的激活，而蛋白质印迹显示JAK2、STAT3、NF-κB p65和IκBα的磷酸化增强，同时IL-17A上调。丙二醛水平升高进一步反映了氧化脂质损伤。这些发现表明，SD通过昼夜节律紊乱和ROS/NLRP3/IL-17A炎症轴的激活加剧了SiNPs诱导的ELG功能障碍。虽然这些影响目前仅限于泪腺，但未来需要研究来确定类似机制是否会导致更广泛的全身代谢后果。
