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香菇多糖对5-氟尿嘧啶诱导的黏膜炎小鼠肠道微生物群和炎性细胞因子的影响

Lentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice.

作者信息

Zhang Xiaoxiao, Wang Liang, Khan Asif Iqbal, Rehman Ata Ur, Khinsar Kavish Hasnain, Xin Yi

机构信息

Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian, 116044, China.

Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.

出版信息

AMB Express. 2025 Jan 22;15(1):11. doi: 10.1186/s13568-024-01796-z.

DOI:10.1186/s13568-024-01796-z
PMID:39843881
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11754778/
Abstract

Chemotherapeutic therapies for cancer are frequently associated with cytotoxic side effects that can be harmful to human health, including the development of intestinal mucositis (IM). It mostly affects the gastrointestinal tract, causing ulceration, inflammation, and the formation of lesions in the colon. Surprisingly, despite the frequency of IM, therapeutic choices remain restricted. In our search for new intestinal mucositis therapies, we wanted to see how Lentinan (LT), derived from Lentinus edodes, would fare in mouse models of intestinal mucositis. To create the intestinal mucositis model in mice, we gave them intra-peritoneal doses of 5-fluorouracil (5-FU) (50 mg/kg) and then tested the effects of Lentinan on intestinal mucositis. This examination required constant monitoring of several factors, such as body weight fluctuations, food consumption, and diarrhea. In addition, we measured the levels of certain inflammatory cytokines (Tumour Necrosis Factor-alpha (TNF-α), Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Interleukin-10 (IL-10), looked at the expression of tight junction proteins (Zonula Occludens-1(ZO-1), Claudin-1), measured mucin-2 levels, and looked into changes in the gut flora. In the mouse model of intestinal mucositis, our findings showed that LT effectively reduced weight loss, increased food intake, and relieved diarrhea. Concurrently, we saw a decrease in the expression of inflammatory cytokines such as TNF-α, IL-1, and IL-6, as well as a considerable increase in the concentration of IL-10. Furthermore, LT reduced intestinal mucositis by increasing the length and structural integrity of the colon. Furthermore, increased expression of tight junction proteins (ZO-1, Claudin-1), mucin-2, and an increase in the number of goblet cells all confirmed our previous findings. Notably, the makeup of beneficial bacteria in the stomach increased as well. Finally, our findings suggest that LT can effectively prevent 5-fluorouracil-induced intestinal mucositis in mice by improving immune function, restoring intestinal barrier integrity, and rebalancing gut microbial flora.

摘要

癌症的化疗疗法常常伴随着对人体健康有害的细胞毒性副作用,包括肠道黏膜炎(IM)的发生。它主要影响胃肠道,导致溃疡、炎症以及结肠病变的形成。令人惊讶的是,尽管IM很常见,但治疗选择仍然有限。在寻找新的肠道黏膜炎治疗方法的过程中,我们想看看来源于香菇的香菇多糖(LT)在肠道黏膜炎小鼠模型中的表现。为了在小鼠中建立肠道黏膜炎模型,我们给它们腹腔注射5-氟尿嘧啶(5-FU)(50毫克/千克),然后测试香菇多糖对肠道黏膜炎的影响。这项检查需要持续监测几个因素,如体重波动、食物摄入量和腹泻情况。此外,我们测量了某些炎性细胞因子(肿瘤坏死因子-α(TNF-α)、白细胞介素-1(IL-1)、白细胞介素-6(IL-6)和白细胞介素-10(IL-10))的水平,观察紧密连接蛋白(闭合蛋白-1(ZO-1)、Claudin-1)的表达,测量黏蛋白-2水平,并研究肠道菌群的变化。在肠道黏膜炎小鼠模型中,我们的研究结果表明,香菇多糖有效地减轻了体重减轻、增加了食物摄入量并缓解了腹泻。同时,我们观察到TNF-α、IL-1和IL-6等炎性细胞因子的表达下降,以及IL-10浓度的显著增加。此外,香菇多糖通过增加结肠的长度和结构完整性减轻了肠道黏膜炎。此外,紧密连接蛋白(ZO-1、Claudin-1)、黏蛋白-2表达的增加以及杯状细胞数量的增加都证实了我们之前的发现。值得注意的是,胃中有益细菌的组成也增加了。最后,我们的研究结果表明,香菇多糖可以通过改善免疫功能、恢复肠道屏障完整性和重新平衡肠道微生物菌群,有效预防5-氟尿嘧啶诱导的小鼠肠道黏膜炎。

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