雜志名稱：Journal of Advanced Research
影響因子：11.4
文章題目：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
作者單位：
浙江大學(xué)動(dòng)物科學(xué)學(xué)院
西北工業(yè)大學(xué)生命科學(xué)與工程學(xué)院
引用YOBIBIO產(chǎn)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.
介紹：生物硒納米顆粒 （SeNPs） 由于其多種生物活性和獨(dú)特的物理化學(xué)性質(zhì)，已成為氧化還原和免疫反應(yīng)等生物反應(yīng)的新型有前途的調(diào)節(jié)劑。
目標(biāo)：本研究的研究目的是探討腸上皮細(xì)胞對(duì) SeNPs 的攝取和代謝機(jī)制及其對(duì)腸道屏障功能的保護(hù)作用。
方法：我們?cè)O(shè)計(jì)了一種腸道芯片來(lái)復(fù)制腸道的關(guān)鍵結(jié)構(gòu)和環(huán)境特征，以研究氧化應(yīng)激對(duì)腸上皮細(xì)胞腸道屏障功能和免疫穩(wěn)態(tài)的影響以及 SeNPs 的調(diào)節(jié)作用，并通過(guò)小鼠和仔豬模型進(jìn)行了驗(yàn)證。
結(jié)果：生物 SeNPs 可通過(guò)網(wǎng)格蛋白和小窩介導(dǎo)的內(nèi)吞作用被 IPEC-J2 細(xì)胞有效吸收，并進(jìn)一步代謝成細(xì)胞內(nèi)的硒代胱氨酸和微量的亞硒酸鹽，然后摻入抗氧化劑硒酶的合成中。腸道芯片模型證實(shí)，敵草快誘導(dǎo)的氧化應(yīng)激顯著損害了腸上皮屏障的完整性并破壞了絨毛樣結(jié)構(gòu)。此外，IPEC-J2 細(xì)胞中的氧化應(yīng)激誘導(dǎo)腸粘膜肥大細(xì)胞 （MCs） 活化以釋放 IL-1β 和 TNF-α，進(jìn)一步加劇 IPEC-J2 細(xì)胞中的氧化應(yīng)激并導(dǎo)致 ROS 過(guò)量產(chǎn)生。然而，SeNPs 處理增加了細(xì)胞硒含量和抗氧化硒酶活性，調(diào)節(jié)了 AMPK/NLRP3/Nrf2 通路，有效緩解了氧化應(yīng)激，維持了線粒體穩(wěn)態(tài)，抑制了促炎因子的表達(dá)。小鼠和早期斷奶仔豬模型進(jìn)一步證實(shí)，SeNPs 可以增加空腸中硒蛋白的表達(dá)，減少 MCs 的活化，抑制細(xì)胞焦亡，并最終對(duì)腸道屏障氧化損傷表現(xiàn)出有效的保護(hù)作用。
結(jié)論：這些結(jié)果表明，生物 SeNPs 增強(qiáng)了抗氧化酶防御，維持了線粒體穩(wěn)態(tài)，抑制了炎癥細(xì)胞與腸上皮細(xì)胞之間的串?dāng)_，從而保護(hù)腸上皮屏障免受氧化應(yīng)激損傷。
