Jing Bolin, Xia Kun, Zhang Chen, Jiao Siming, Zhu Limeng, Wei Jinhua, Wang Zhuo A, Chen Nannan, Tu Pengfei, Li Jianjun, Du Yuguang
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Front Cell Dev Biol. 2022 Apr 26;10:877892. doi: 10.3389/fcell.2022.877892. eCollection 2022.
Past studies on the protective effects of chitosan oligosaccharides (COS) on inflammatory bowel disease (IBD) commonly rely on animal models, because traditional cell culture systems couldn't faithfully mimic human intestinal physiology. Here a novel human gut-on-a-chip microsystem was established to further explore the regulatory effects of COS on the occurrence and development of human enteritis. By constructing an intestinal injury model caused by dextran sodium sulfate (DSS) on the chip, this study proved that COS can reduce intestinal epithelial injury by promoting the expression of the mucous layer for the first time. By establishing an inflammatory bowel disease model on the chip caused by 11775, this study demonstrated that COS can protect the intestinal epithelial barrier and vascular endothelial barrier by inhibiting the adhesion and invasion of 11775 for the first time. In addition, similar to the results COS can decrease the inflammatory response by reducing the expression of toll-like receptor 4 protein and reducing the nuclear DNA binding rate of nuclear factor kappa-B protein on this chip. In summary, COS can be used as a potential drug to treat human IBD and the human gut-on-a-chip would be used as a platform for quick screening drugs to treat human IBD in future.
过去关于壳寡糖(COS)对炎症性肠病(IBD)保护作用的研究通常依赖动物模型,因为传统的细胞培养系统无法忠实地模拟人类肠道生理。在此,建立了一种新型的人体肠道芯片微系统,以进一步探索COS对人类肠炎发生发展的调节作用。通过在芯片上构建由葡聚糖硫酸钠(DSS)引起的肠道损伤模型,本研究首次证明COS可通过促进黏液层表达来减轻肠道上皮损伤。通过在芯片上建立由11775引起的炎症性肠病模型,本研究首次证明COS可通过抑制11775的黏附和侵袭来保护肠道上皮屏障和血管内皮屏障。此外,与在该芯片上的结果类似,COS可通过降低Toll样受体4蛋白表达和降低核因子κB蛋白的核DNA结合率来减轻炎症反应。总之,COS可作为治疗人类IBD的潜在药物,未来人体肠道芯片将作为快速筛选治疗人类IBD药物的平台。