Abstract

Context

Modified BuShenYiQi formula (M-BYF) is derived from BuShenYiQi formula, used for the treatment of allergic asthma. The exact effect and mechanism of M-BYF on the improvement of asthma remain unclear.

Objective

We investigated the mechanism underlying the therapeutic effect of M-BYF on allergic asthma.

Materials and methods

The asthma model was established in female BALB/c mice that were sensitized and challenged with ovalbumin (OVA). Mice in the treated groups were orally treated once a day with M-BYF (7, 14 and 28 g/kg/d) or dexamethasone before OVA challenge. Control and Model group received saline. Pathophysiological abnormalities and percentages of lung type 2 innate lymphoid cells (ILC2s) and Th9 cells were measured. Expression levels of type 2 cytokines and transcription factors required for these cells function and differentiation were analysed. Expression of vasoactive intestinal polypeptide (VIP)–VPAC2 signalling pathway-related proteins, and percentages of VIP expressing (VIP⁺) cells and VPAC2, CD90 co-expressing (VPAC2⁺CD90⁺) cells were detected.

Results

M-BYF alleviated airway hyperresponsiveness, inflammation, mucus hypersecretion and collagen deposition in asthmatic mice. M-BYF down-regulated percentages of ILC2s and Th9 cells with lower expression of GATA3, PU.1 and IRF4, reduced IL-5, IL-13, IL-9 and VIP production. The decrease in the expression of VIP–VPAC2 signalling pathway and percentages of VIP⁺ cells, VPAC2⁺CD90⁺ cells were observed after M-BYF treatment. The LD₅₀ value of M-BYF was higher than 90 g/kg.

Discussion and conclusions

M-BYF alleviated experimental asthma by negatively regulating ILC2s and Th9 cells and the VIP–VPAC2 signalling pathway. These findings provide the theoretical basis for future research of M-BYF in asthma patient population.

中文翻译：

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补肾益气方通过负调控2型先天性淋巴细胞和CD4+ 9型辅助性T细胞及VIP-VPAC2信号通路减轻小鼠实验性过敏性哮喘

摘要

语境

补肾益气方（M-BYF）来源于补肾益气方，用于治疗过敏性哮喘。M-BYF改善哮喘的确切作用和机制尚不清楚。

客观的

我们研究了 M-BYF 治疗过敏性哮喘的潜在机制。

材料和方法

哮喘模型是在雌性 BALB/c 小鼠中建立的，这些小鼠用卵清蛋白 (OVA) 致敏和攻击。在 OVA 攻击之前，治疗组中的小鼠每天口服一次 M-BYF（7、14 和 28 g/kg/d）或地塞米松。对照组和模型组接受生理盐水。测量了肺 2 型先天淋巴细胞 (ILC2s) 和 Th9 细胞的病理生理异常和百分比。分析了这些细胞功能和分化所需的 2 型细胞因子和转录因子的表达水平。检测血管活性肠多肽（VIP）-VPAC2信号通路相关蛋白的表达，以及VIP表达（VIP ⁺）细胞和VPAC2、CD90共表达（VPAC2 ⁺ CD90 ⁺）细胞的百分比。

结果

M-BYF 减轻哮喘小鼠的气道高反应性、炎症、粘液分泌过多和胶原蛋白沉积。M-BYF 下调 ILC2 和 Th9 细胞的百分比，GATA3、PU.1 和 IRF4 表达降低，减少 IL-5、IL-13、IL-9 和 VIP 的产生。M-BYF处理后观察到VIP-VPAC2信号通路的表达和VIP ⁺细胞、VPAC2 ⁺ CD90 ^{+细胞的百分比降低。}M-BYF的LD ₅₀值高于90 g/kg。

讨论和结论

M-BYF 通过负调节 ILC2s 和 Th9 细胞以及 VIP-VPAC2 信号通路来缓解实验性哮喘。这些发现为未来在哮喘患者人群中研究M-BYF提供了理论基础。