Zhao Lei, Yu Jie, Liu Yunzhuo, Liu Yihan, Zhao Yiran, Li Mu-Yang
College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, China; Key Laboratory of Efficient Utilization of Feed Resources and Nutrition Manipulation in Cold Region of Heilongjiang Province, Daqing, Heilongjiang 163319, China; Key Laboratory of Low-carbon Green Agriculture in Northeastern China, Ministry of Agriculture and Rural Affairs PR China, Daqing, Heilongjiang 163319, China.
College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, China.
Int J Biol Macromol. 2025 Mar;296:139710. doi: 10.1016/j.ijbiomac.2025.139710. Epub 2025 Jan 9.
Acute enteritis, an intestinal disease with intestinal inflammation and injury as the main pathological manifestations. Inhibiting the inflammatory response is critical to the treatment of acute enteritis. Previous studies have shown that the Hippophae rhamnoides polysaccharide (HRP) has strong immune-enhancing effects. However, their functions regarding the intestines and the underlying mechanism are still unclear. In this study, the role of HRP in lipopolysaccharide (LPS)-induced acute enteritis in mice and its related mechanisms are discussed from two aspects: intestinal inflammation and intestinal microbiota. Kunming mice were inoculated with LPS to establish animal models of acute enteritis. The results showed that HRP attenuated the histological damage and maintained the intestine mucosal barrier via up-regulating the expression of occludin, claudin-1, and zona occludens-1 (ZO-1), and suppressing the levels of pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)). The relative mRNA and protein levels of nuclear factor-kappa B p65 (NF-κBp65) and tumor necrosis factor-receptor-associated factor 6 (TRAF6) in the intestine tissues of LPS-induced acute enteritis mice significantly increased, whereas these adverse changes were alleviated in the HRP intervention groups. Notably, HRP may regulate the expression of the TRAF6/NF-κB signaling pathway by affecting the diversity of the intestinal microbiota. Microbiota analysis showed that HRP promoted the proliferation of beneficial bacteria, including Clostridia_UCG-014, Candidatus_Saccharimonas, Lachnospiraceae_NK4A136_group, Bacteroidota, Deferribacterota, and reduced the abundance of Atopostipes, Corynebacterium, Actinobacteriota, and Desulfobacterota. The studies conformed that the gut microbiota is crucial in HRP-mediated immunity regulation. HRP shows great potential as an immune enhancer and a natural medicine for treating intestinal inflammatory diseases.
急性肠炎是一种以肠道炎症和损伤为主要病理表现的肠道疾病。抑制炎症反应对急性肠炎的治疗至关重要。以往研究表明，沙棘多糖（HRP）具有较强的免疫增强作用。然而，其对肠道的作用及潜在机制仍不清楚。本研究从肠道炎症和肠道微生物群两个方面探讨了HRP在脂多糖（LPS）诱导的小鼠急性肠炎中的作用及其相关机制。将昆明小鼠接种LPS以建立急性肠炎动物模型。结果表明，HRP通过上调闭合蛋白、紧密连接蛋白-1和闭合小带蛋白-1（ZO-1）的表达，并抑制促炎细胞因子（肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β））的水平，减轻了组织学损伤并维持了肠道黏膜屏障。LPS诱导的急性肠炎小鼠肠道组织中核因子-κB p65（NF-κBp65）和肿瘤坏死因子受体相关因子6（TRAF6）的相对mRNA和蛋白水平显著升高，而在HRP干预组中这些不良变化得到缓解。值得注意的是，HRP可能通过影响肠道微生物群的多样性来调节TRAF6/NF-κB信号通路的表达。微生物群分析表明，HRP促进了有益菌的增殖，包括梭菌属_UCG-014、候选糖单胞菌属、毛螺菌科_NK4A136_group、拟杆菌门、脱铁杆菌门，并降低了阿托波氏菌属、棒状杆菌属、放线菌门和脱硫杆菌门的丰度。研究证实肠道微生物群在HRP介导的免疫调节中至关重要。HRP作为一种免疫增强剂和治疗肠道炎症性疾病的天然药物具有巨大潜力。
