加味葛根芩连汤通过恢复肠道黏液屏障和抑制γδT17 细胞的激活来改善 DSS 诱导的小鼠慢性结肠炎。

Modified Gegen Qinlian decoction ameliorates DSS-induced chronic colitis in mice by restoring the intestinal mucus barrier and inhibiting the activation of γδT17 cells.

机构信息

Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China.

Department of Gastroenterology, Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), 100091, Beijing, China.

出版信息

Phytomedicine. 2023 Mar;111:154660. doi: 10.1016/j.phymed.2023.154660. Epub 2023 Jan 12.

DOI:10.1016/j.phymed.2023.154660

PMID:36681051

Abstract

BACKGROUND

Current therapeutics for ulcerative colitis (UC) have limitations. Classical Formula Gegen Qinlian decoction (GQD) is derived from Shang Han Lun and has a long history of treating gastrointestinal diseases such as diarrhea and UC. Nevertheless, the exact mechanism of it needs to be further clarified.

PURPOSE

We aimed to investigate the treatment effects of modified GQD (MGQD) on dextran sodium sulfate (DSS)-induced chronic colitis in mice and conduct further exploration of its underlying mechanisms.

METHODS

The protective effect of MGQD was estimated in a DSS-induced chronic colitis mouse model. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Alcian Blue/Phosphoric Acid Schiff (AB/PAS) staining, transmission electron microscopy (TEM), immunofluorescence and real time‒PCR (RT-PCR) were used to assess goblet cell function. ELISA, flow cytometry and immunofluorescence were applied to estimate the immunoinflammatory status. Western blot was performed to test the protein expression levels of relevant pathways and related receptors. All experiments were conducted in duplicate.

RESULTS

MGQD alleviated DSS‑induced chronic colitis symptoms in mice, protected goblet cell function and restored the intestinal mucus barrier. Furthermore, MGQD efficiently suppressed the abnormal immune inflammatory response and the activate of γδT17 cells and NLRP3 inflammasome.

CONCLUSION

The mechanisms by which MGQD protects against DSS-induced chronic colitis may involve restoring goblet cell function, repairing the intestinal mucus barrier, and modulating the immune inflammatory response. More importantly, MGQD inhibited NLRP3 inflammasome-associated signaling pathway activation, which consequently reduced the activation of γδT17 cells.

摘要

背景

目前溃疡性结肠炎（UC）的治疗方法存在局限性。经典方葛根芩连汤（GQD）源于《伤寒论》，用于治疗腹泻和 UC 等胃肠道疾病已有很长的历史。然而，其确切机制仍需进一步阐明。

目的

本研究旨在探讨改良葛根芩连汤（MGQD）对葡聚糖硫酸钠（DSS）诱导的慢性结肠炎小鼠的治疗作用，并进一步探讨其作用机制。

方法

在 DSS 诱导的慢性结肠炎小鼠模型中评估 MGQD 的保护作用。模型评估包括体重、疾病活动指数（DAI）评分、结肠长度和组织病理学。使用阿尔新蓝/磷钨酸 Schiff（AB/PAS）染色、透射电子显微镜（TEM）、免疫荧光和实时-PCR（RT-PCR）评估杯状细胞功能。ELISA、流式细胞术和免疫荧光法用于评估免疫炎症状态。Western blot 用于检测相关通路和相关受体的蛋白表达水平。所有实验均重复进行。