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加味葛根芩连汤通过调节肠道微生物群和胆汁酸代谢,恢复溃疡性结肠炎小鼠模型中杯状细胞的功能。

Modified Gegen Qinlian Decoction modulated the gut microbiome and bile acid metabolism and restored the function of goblet cells in a mouse model of ulcerative colitis.

机构信息

Department of Gastroenterology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.

Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Front Immunol. 2024 Aug 6;15:1445838. doi: 10.3389/fimmu.2024.1445838. eCollection 2024.

Abstract

OBJECTIVE

Modified Gegen Qinlian Decoction (MGQD) has been shown to effectively relieve ulcerative colitis (UC) without a known pharmacological mechanism. In this study, the anti-colitis efficaciousness of MGQD and its underlying mechanisms in UC were evaluated.

METHODS

Mice with colitis were administered MGQD for 7 days. Following the evaluation of clinical symptoms, gut microbiota in the feces of UC mice was examined using 16S rRNA sequencing and bile acids (BAs) were examined using LC/MS. Gut microbiota consumption and fecal microbiota transplantation (FMT) were used to explore the involvement of gut microbiota in the anti-UC action of MGQD.

RESULTS

MGQD relieved colitis as shown by weight loss protection, a lower disease activity index (DAI), restoration of intestinal length reduction, and lower histopathologic scores. MGQD also restored crypt stem cell proliferation and function of colonic goblet cells, and promoted MUC2 protein secretion. Interestingly, investigations using gut bacterial depletion and FMT showed that MGQD attenuated colonic damage in a gut-dependent way. The modulation of the gut microbiota by MGQD might be attributed to a decrease in and an increase in n. In addition, MGQD modulated the metabolism of BAs while restoring the structure of the gut microbiota.

CONCLUSION

MGQD significantly alleviated colitis in mice, which may be associated with the modulation of gut microbiota and BA metabolism and restoration of function of goblet cells. However, factors other than the gut microbiota may also be involved in the amelioration of UC by MGQD.

摘要

目的

加味葛根芩连汤(MGQD)已被证明可有效缓解溃疡性结肠炎(UC),但其确切的药理机制尚不清楚。本研究旨在评估 MGQD 对 UC 的治疗作用及其潜在机制。

方法

采用葡聚糖硫酸钠(DSS)诱导建立 UC 模型,MGQD 灌胃给药 7 天。观察疾病活动指数(DAI)、结肠组织病理学变化、结肠长度等,评估 MGQD 对 UC 的治疗作用;采用 16S rRNA 测序技术分析粪便菌群结构,采用 LC/MS 分析胆汁酸(BA)代谢谱,评估 MGQD 对 UC 模型肠道菌群和 BA 代谢的影响;通过抗生素灌胃、粪菌移植(FMT)等方法,研究 MGQD 对 UC 的治疗作用是否依赖于肠道菌群。

结果

MGQD 可显著改善 DSS 诱导的 UC 模型小鼠的体重下降、DAI 评分、结肠缩短等临床症状,减轻结肠组织病理损伤,促进隐窝干细胞增殖和杯状细胞分泌功能,其作用可能与调节肠道菌群和胆汁酸代谢有关。进一步研究发现,MGQD 可增加 UC 模型小鼠肠道中拟杆菌门(Bacteroidetes)相对丰度,降低厚壁菌门(Firmicutes)丰度,增加有益代谢产物次级胆汁酸(n)的含量,降低有害代谢产物初级胆汁酸()的含量,同时改善肠道菌群结构。此外,MGQD 还可通过调控肠道菌群改善 UC 模型小鼠的 BA 代谢,促进 MUC2 蛋白分泌。MGQD 减轻 UC 模型小鼠结肠损伤的作用可能依赖于肠道菌群,通过抗生素灌胃或粪菌移植(FMT)处理可部分阻断 MGQD 的治疗作用。

结论

加味葛根芩连汤可显著缓解 UC 模型小鼠的结肠损伤,其作用机制可能与调节肠道菌群和胆汁酸代谢、改善杯状细胞功能有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0e7/11333261/915a6b2ea8d5/fimmu-15-1445838-g001.jpg

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