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源自调节性T细胞的负载氧化铈外泌体通过清除活性氧和调节炎症反应改善炎症性肠病。

Cerium Oxide-Loaded Exosomes Derived From Regulatory T Cells Ameliorate Inflammatory Bowel Disease by Scavenging Reactive Oxygen Species and Modulating the Inflammatory Response.

作者信息

Yue Simei, Gong Lingjiao, Tan Yulin, Zhang Xiaodan, Liao Fei

机构信息

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000, People's Republic of China.

Wuhan University Shenzhen Research Institute, Shenzhen, Guangdong, 518000, People's Republic of China.

出版信息

J Inflamm Res. 2025 Mar 25;18:4395-4408. doi: 10.2147/JIR.S502388. eCollection 2025.

DOI:10.2147/JIR.S502388
PMID:40162080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11954482/
Abstract

BACKGROUND

Abnormal immune homeostasis, which leads to the accumulation of reactive oxygen species (ROS) and an inflammatory response, plays a crucial role in accelerating the progression of inflammatory bowel disease (IBD). The lack of targeted therapeutic strategies significantly hampers the efficacy of clinical treatments for IBD. This study presents cerium oxide nanoparticle-loaded regulatory T cell-derived exosomes (exo@nCeO) as innovative anti-inflammatory and antioxidant agents specifically designed to address the effects of immune dysregulation.

METHODS

In this work, the morphology and antioxidant properties of nano-cerium oxide were characterized using transmission electron microscopy, as well as hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl radical assays. Tumor necrosis factor-α and dextran sulfate sodium were employed to establish cellular and animal models of IBD. The impact of exo@nCeO on ROS scavenging and anti-inflammatory activity in intestinal epithelial cells was assessed using dihydroethidium and 2,7-dichlorodihydrofluorescein staining, Western blotting, and apoptosis flow cytometry analysis. Hematoxylin and eosin staining, along with immunohistochemistry and immunofluorescence staining, were utilized to evaluate intestinal epithelial inflammation and ROS levels in the IBD mouse model.

RESULTS

The findings demonstrate that exo@nCeO possesses augmented anti-inflammatory properties and ROS scavenging abilities in intestinal epithelial cells. In murine models of IBD, exo@nCeO effectively maintained the integrity of the intestinal epithelial barrier and impeded the progression of IBD.

CONCLUSION

This study introduces a novel therapeutic approach for IBD and underscores a potential strategy for addressing diseases associated with inflammation and oxidative stress.

摘要

背景

异常的免疫稳态会导致活性氧(ROS)积累和炎症反应,在加速炎症性肠病(IBD)进展中起关键作用。缺乏靶向治疗策略严重阻碍了IBD临床治疗的疗效。本研究提出负载氧化铈纳米颗粒的调节性T细胞衍生外泌体(exo@nCeO)作为专门设计用于解决免疫失调影响的创新抗炎和抗氧化剂。

方法

在本研究中,使用透射电子显微镜以及羟基自由基和1,1-二苯基-2-苦基肼自由基测定法对纳米氧化铈的形态和抗氧化性能进行了表征。采用肿瘤坏死因子-α和葡聚糖硫酸钠建立IBD的细胞和动物模型。使用二氢乙锭和2,7-二氯二氢荧光素染色、蛋白质印迹法和凋亡流式细胞术分析评估exo@nCeO对肠上皮细胞中ROS清除和抗炎活性的影响。苏木精和伊红染色以及免疫组织化学和免疫荧光染色用于评估IBD小鼠模型中的肠上皮炎症和ROS水平。

结果

研究结果表明,exo@nCeO在肠上皮细胞中具有增强的抗炎特性和ROS清除能力。在IBD小鼠模型中,exo@nCeO有效地维持了肠上皮屏障的完整性并阻碍了IBD的进展。

结论

本研究为IBD引入了一种新的治疗方法,并强调了一种解决与炎症和氧化应激相关疾病的潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5804/11954482/6e8c89bd71c9/JIR-18-4395-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5804/11954482/e4f89c78f8b0/JIR-18-4395-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5804/11954482/e5ce7a64a5c4/JIR-18-4395-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5804/11954482/6f04218ee876/JIR-18-4395-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5804/11954482/b26adde96dd7/JIR-18-4395-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5804/11954482/6e8c89bd71c9/JIR-18-4395-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5804/11954482/e4f89c78f8b0/JIR-18-4395-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5804/11954482/e5ce7a64a5c4/JIR-18-4395-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5804/11954482/6f04218ee876/JIR-18-4395-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5804/11954482/b26adde96dd7/JIR-18-4395-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5804/11954482/6e8c89bd71c9/JIR-18-4395-g0005.jpg

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