Li Jian-Hong, Xu Jing, Huang Chen, Hu Jin-Xia, Xu Hao-Ming, Guo Xue, Zhang Yan, Xu Jing-Kui, Peng Yao, Zhang Yong, Zhu Min-Zheng, Zhou You-Lian, Nie Yu-Qiang
Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People's Republic of China.
Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, People's Republic of China.
Int J Nanomedicine. 2024 Dec 27;19:13991-14018. doi: 10.2147/IJN.S493434. eCollection 2024.
Plant-derived exosome-like nanoparticles (PELNs) have received widespread attention in treating ulcerative colitis (UC). However, the role of -derived exosome-like nanoparticles (HELNs) in UC remains unclear. This study aims to evaluate the efficacy of HELNs in treating colitis in mice and investigate its potential mechanisms.
HELNs were isolated from for characterization, and their safety and stability were evaluated. A dextran sulfate sodium (DSS)-induced colitis mouse model was utilized to assess the therapeutic potential of HELNs in UC. In vivo, imaging and flow cytometry were utilized to investigate the targeting effect of HELNs on inflamed colonic sites and their modulation of the immune environment. RNA-seq analysis and molecular docking were performed to identify potential pathways recruited by HELNs. Guided by transcriptomic findings, NLRP3 mice were used in conjunction with Western blotting, qPCR, immunofluorescence, and other techniques to verify that HELNs alleviated DSS-induced colitis by inhibiting NLRP3/NOD-like receptor signaling pathways. Lastly, the impact of HELNs on the gut microbiota was investigated through 16S rRNA sequencing.
HELNs significantly reduced the severity of DSS-induced colitis in mice, alleviating colitis symptoms and histopathological damage. Furthermore, HELNs can specifically target inflamed colon tissue, regulate the immune environment, and decrease inflammation. RNA-seq analysis, coupled with the use of NLRP3 mice, demonstrated that HELNs inhibited the NLRP3/NOD-like receptor signaling pathways. Lastly, HELNs balanced the gut microbiota composition in mice with colitis, decreasing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria in the intestinal tract of these mice.
In summary, HELNs exhibit the potential to protect the colon from DSS-induced damage by inhibiting the NLRP3/NOD-like receptor signaling pathway and modulating the gut microbiota, presenting a promising therapeutic option for the management of UC.
植物源外泌体样纳米颗粒（PELNs）在治疗溃疡性结肠炎（UC）方面受到广泛关注。然而，人源外泌体样纳米颗粒（HELNs）在UC中的作用仍不清楚。本研究旨在评估HELNs治疗小鼠结肠炎的疗效并探究其潜在机制。
从人源中分离出HELNs进行表征，并评估其安全性和稳定性。利用葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型评估HELNs在UC中的治疗潜力。在体内，利用成像和流式细胞术研究HELNs对炎症结肠部位的靶向作用及其对免疫环境的调节。进行RNA测序分析和分子对接以确定HELNs募集的潜在途径。在转录组学研究结果的指导下，将NLRP3小鼠与蛋白质免疫印迹、定量聚合酶链反应、免疫荧光及其他技术结合使用，以验证HELNs通过抑制NLRP3/核苷酸结合寡聚化结构域样受体信号通路减轻DSS诱导的结肠炎。最后，通过16S核糖体RNA测序研究HELNs对肠道微生物群的影响。
HELNs显著降低了DSS诱导的小鼠结肠炎的严重程度，减轻了结肠炎症状和组织病理学损伤。此外，HELNs可特异性靶向炎症结肠组织，调节免疫环境并减轻炎症。RNA测序分析以及使用NLRP3小鼠表明，HELNs抑制了NLRP3/核苷酸结合寡聚化结构域样受体信号通路。最后，HELNs平衡了结肠炎小鼠的肠道微生物群组成，降低了有害细菌的丰度并增加了这些小鼠肠道中有益细菌的丰度。
总之，HELNs具有通过抑制NLRP3/核苷酸结合寡聚化结构域样受体信号通路和调节肠道微生物群来保护结肠免受DSS诱导损伤的潜力，为UC的治疗提供了一个有前景的治疗选择。
