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索罗蓝保汤通过抑制 IL-13/STAT6 信号通路抑制香烟烟雾诱导的气道炎症和黏蛋白 5AC 过度分泌对大鼠发挥作用。

Srolo Bzhtang, a traditional Tibetan medicine formula, inhibits cigarette smoke induced airway inflammation and muc5ac hypersecretion via suppressing IL-13/STAT6 signaling pathway in rats.

机构信息

Research Center for High Altitude Medicine, Qinghai University, Xining 810001, China; Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province, Xining 810001, China.

Xining Customs District, Key Laboratory of Food Safety Research in Qinghai Province, Xining 810003, China.

出版信息

J Ethnopharmacol. 2019 May 10;235:424-434. doi: 10.1016/j.jep.2019.02.006. Epub 2019 Feb 5.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Srolo Bzhtang (SBT), a traditional Tibetan medicine formula, was composed of three herbs, Solms-Laubachia eurycarpa, Bergenia purpurascens, Glycyrrhiza uralensis, and one lac, and was first documented in the ancient Tibetan medical work Four Medical Tantras (rGyud-bzhi) in the eighth century AD. It has been widely used to treat lung "phlegm-heat" syndromes such as chronic bronchitis and chronic obstructive pulmonary disease (COPD).

OBJECTIVE

The aim of this study was to evaluate the potential influences of aqueous extract of SBT on airway inflammation and mucus secretion and to reveal the underlying mechanism in a rat model of cigarette smoke (CS)-induced chronic bronchitis (CB).

MATERIALS AND METHODS

Sixty male Sprague-Dawley rats were randomly divided to six groups: control (room air exposure), model (CS exposure), DEX (CS exposure and 0.2 mg/kg/day dexamethasone), and three SBT (CS exposure and 1.67, 2.50, and 3.34 g/kg/day SBT) groups. DEX and the three doses of SBT were administered by oral gavage every day for eight weeks. Pathological changes and mucus expression in the lung tissue were determined by hematoxylin and eosin (H&E), Alcian blue-periodic acid-Schiff (AB-PAS) and immunohistochemical staining. The levels of cytokines in bronchoalveolar lavage fluid (BALF) were assessed by ELISA. Western blot analysis and qRT-PCR were performed to explore the effects of SBT on the expression of IL-13, STAT6 and MUC5AC.

RESULTS

Pretreatment with SBT attenuated the TNF-α, IL-8, IL-13 expression levels in BALF and the inflammatory cell infiltration in bronchial walls and peribronchial lung tissue. SBT exhibited a dose-dependent downregulation of MUC5AC expression as assessed by AB-PAS and immunohistochemical staining. The protein and mRNA levels of IL-13, STAT6/p-STAT6 and MUC5AC were also downregulated by SBT preconditioning.

CONCLUSION

These results for the first time demonstrated that SBT exhibited protective effects on CS-induced airway inflammation and MUC5AC hypersecretion, which might be related to the downregulation of the IL-13/STAT6 signaling pathway.

摘要

民族药理学相关性

Srolo Bzhtang(SBT)是一种传统的藏药配方,由三种草药 Solms-Laubachia eurycarpa、Bergenia purpurascens、Glycyrrhiza uralensis 和一种干酪素组成,最早记录在公元 8 世纪的藏医四部医典(rGyud-bzhi)中。它已被广泛用于治疗慢性支气管炎和慢性阻塞性肺疾病(COPD)等肺部“痰热”综合征。

目的

本研究旨在评估 SBT 水提物对气道炎症和黏液分泌的潜在影响,并揭示其在香烟烟雾(CS)诱导的慢性支气管炎(CB)大鼠模型中的潜在机制。

材料和方法

60 只雄性 Sprague-Dawley 大鼠随机分为 6 组:对照组(空气暴露)、模型组(CS 暴露)、DEX 组(CS 暴露和 0.2mg/kg/天地塞米松)和 SBT 三个剂量组(CS 暴露和 1.67、2.50 和 3.34g/kg/天 SBT)。DEX 和三种剂量的 SBT 通过口服灌胃每天给药 8 周。通过苏木精和伊红(H&E)、阿尔辛蓝-过碘酸-希夫(AB-PAS)和免疫组织化学染色来确定肺组织中的病理变化和黏液表达。通过 ELISA 评估支气管肺泡灌洗液(BALF)中的细胞因子水平。Western blot 分析和 qRT-PCR 用于探索 SBT 对 IL-13、STAT6 和 MUC5AC 表达的影响。

结果

SBT 预处理可减轻 BALF 中 TNF-α、IL-8、IL-13 的表达水平以及支气管壁和支气管周围肺组织中的炎症细胞浸润。SBT 表现出剂量依赖性下调 MUC5AC 表达,通过 AB-PAS 和免疫组织化学染色评估。SBT 预处理还下调了 IL-13、STAT6/p-STAT6 和 MUC5AC 的蛋白和 mRNA 水平。

结论

这些结果首次表明,SBT 对 CS 诱导的气道炎症和 MUC5AC 过度分泌具有保护作用,这可能与 IL-13/STAT6 信号通路的下调有关。

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