杂志名称：Journal of Advanced Research
影响因子：11.4
文章题目：Prophylactic supplementation with biogenic selenium nanoparticles mitigated intestinal barrier oxidative damage through suppressing epithelial-immune crosstalk with gut-on-a-chip
DOI：https://doi.org/10.1016/j.jare.2025.04.023
第一作者：Lei Qiao, Ge Yang, Tianjing Deng, Jiajing Chang, Xina Dou, Xiaofan Song, Xiaonan Zeng, Li Ren, Chunlan Xu
作者单位：
浙江大学动物科学学院
西北工业大学生命科学与工程学院
引用YOBIBIO产品：
U96-9810E  Porcine IL-18 Elisa Kit
U96-3716E  Human TNF-α Elisa Kit

文章摘要：
Introduction：Biogenic selenium nanoparticles (SeNPs) have emerged as novel promising modulators of biological reactions such as redox and immune responses due to their multiple bioactivities and unique physicochemical properties.
Objectives：The research objective of this investigation is to explore the mechanism of uptake and metabolism of SeNPs by intestinal epithelial cells and its protective effect on intestinal barrier function with gut-on-a-chip.
Methods：We designed a gut-on-a-chip to replicate key structural and environmental features of the intestinal tract to investigate the effects of oxidative stress on the intestinal barrier function and immune homeostasis of the intestinal epithelial cells as well as the regulatory role of SeNPs, and verified it through mice and piglet models.
Results：Biogenic SeNPs can be effectively taken up by IPEC-J2 cells via clathrin- and caveolae-mediated endocytosis and further metabolized into selenocystine and trace amounts of selenite within cells, which are then incorporated into the synthesis of antioxidant selenoenzymes. A gut-on-a-chip model confirmed that Diquat-induced oxidative stress significantly impaired intestinal epithelial barrier integrity and damaged villi-like structures. In addition, the oxidative stress in IPEC-J2 cells induced activation of intestinal mucosal mast cells (MCs) to release IL-1β and TNF-α, further exacerbating oxidative stress in IPEC-J2 cells and leading to excessive ROS generation. However, SeNPs treatment increased cellular selenium content and antioxidant selenoenzyme activities, modulated AMPK/NLRP3/Nrf2 pathways, effectively alleviated oxidative stress, maintained mitochondrial homeostasis, inhibited pro-inflammatory factors expression. The mice and early-weaned piglet models further confirmed that SeNPs can increase the selenoproteins expression in the jejunum, reduce MCs activation, inhibited cell pyroptosis, and eventually exhibit an effective protective effect against intestinal barrier oxidative damage.
Conclusions：These results indicated that biogenic SeNPs reinforced antioxidant enzyme defenses, maintained mitochondrial homeostasis, inhibited crosstalk between inflammatory cells and intestinal epithelial cells, thereby protecting the intestinal epithelial barrier against oxidative stress damage.
介绍：生物硒纳米颗粒 （SeNPs） 由于其多种生物活性和独特的物理化学性质，已成为氧化还原和免疫反应等生物反应的新型有前途的调节剂。 
目标：本研究的研究目的是探讨肠上皮细胞对 SeNPs 的摄取和代谢机制及其对肠道屏障功能的保护作用。 
方法：我们设计了一种肠道芯片来复制肠道的关键结构和环境特征，以研究氧化应激对肠上皮细胞肠道屏障功能和免疫稳态的影响以及 SeNPs 的调节作用，并通过小鼠和仔猪模型进行了验证。 
结果：生物 SeNPs 可通过网格蛋白和小窝介导的内吞作用被 IPEC-J2 细胞有效吸收，并进一步代谢成细胞内的硒代胱氨酸和微量的亚硒酸盐，然后掺入抗氧化剂硒酶的合成中。肠道芯片模型证实，敌草快诱导的氧化应激显着损害了肠上皮屏障的完整性并破坏了绒毛样结构。此外，IPEC-J2 细胞中的氧化应激诱导肠粘膜肥大细胞 （MCs） 活化以释放 IL-1β 和 TNF-α，进一步加剧 IPEC-J2 细胞中的氧化应激并导致 ROS 过量产生。然而，SeNPs 处理增加了细胞硒含量和抗氧化硒酶活性，调节了 AMPK/NLRP3/Nrf2 通路，有效缓解了氧化应激，维持了线粒体稳态，抑制了促炎因子的表达。小鼠和早期断奶仔猪模型进一步证实，SeNPs 可以增加空肠中硒蛋白的表达，减少 MCs 的活化，抑制细胞焦亡，并最终对肠道屏障氧化损伤表现出有效的保护作用。 

结论：这些结果表明，生物 SeNPs 增强了抗氧化酶防御，维持了线粒体稳态，抑制了炎症细胞与肠上皮细胞之间的串扰，从而保护肠上皮屏障免受氧化应激损伤。