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可以通过促进ILC3和肠道菌群之间的相互作用来恢复肠道屏障功能障碍
Shaowei Huang1, Qiujuan Ye2, Anjiang Wang1
1Integrative Microecology Clinical Center, Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease, Shenzhen Clinical Research Center for Digestive Disease, Shenzhen Technology Research Center of Gut Microbiota Transplantation, Shenzhen Hospital, Southern Medical University, Shenzhen, PR China.
(Paeoniae decoction,PD) 通过增强肠道菌群和3组先天性淋巴细胞 (ILC3) 相互作用来修复性结肠炎中肠道屏障损伤. 这种机制涉及激活质受体 (AHR) 为粘膜愈合的信号通路.
科学领域:
- 胃肠道学和免疫学
- 自然产品药理学 自然产品药理学
- 微生物组研究 微生物组研究
背景情况:
- 肠道屏障功能障碍加剧了性结肠炎 (UC) 的复发和折射性.
- 调节3组先天性淋巴细胞 (ILC3) 和肠道微生物群的相互作用对于UC的粘膜修复至关重要.
- 作为一种传统的UC治疗方法,Paeoniae脱 (PD) 的精确机制在很大程度上仍未被定义.
研究的目的:
- 在慢性结肠炎模型中,评估Paeoniae蒸 (PD) 对硫酸 (DSS) 诱导的肠粘膜损伤的保护作用.
- 阐明PD在慢性结肠炎中发挥治疗作用的潜在分子机制.
主要方法:
- 在C57BL/6小鼠中,使用DSS诱导慢性结肠炎,然后用不同剂量的PD治疗.
- 通过体重,结肠长度,病理评分,炎症标志物 (IL-6,IL-1β),紧结蛋白 (ZO-1,Occludin),IL-22,MUC2和ILC3种群来评估有效性.
- 使用PD的化学分析,网络药理学,体外细胞测定 (MNK-3,NCM460),体外发酵和16SrDNA测序来确定机制和肠道菌群的影响.
主要成果:
- 在大肠炎小鼠中,PD治疗显著改善了体重,结肠长度,并减少了炎症和病理损伤.
- PD上调了MUC2,ZO-1,奥克卢丁和IL-22的表达,增加了ILC3和NCR+ILC3的比率,并调节了肠道微生物群,显著增加了乳杆菌的丰富性.
- 网络药理学确定了基碳化合物受体 (AHR) 信号通路作为关键标,由体外和发酵研究证实,证明PD在激活ILC3-介导的粘膜修复中的作用.
结论:
- (Paeoniae decoction,PD) 通过调节肠道菌群和ILC3相互作用,有效地修复慢性结肠炎中肠道粘膜损伤.
- PD的治疗机制涉及到基碳化合物受体 (AHR) 信号通路的激活.
- PD代表了性结肠炎的有前途的治疗剂,向宿主免疫反应和肠道微生物群.
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