平喘方通过外泌体miR-21-5p调控TGF-β/Smad2/3信号通路对哮喘小鼠气道重塑的保护作用*

作者：顾静雯1，傅 伟1，顾昳衡1，董晨洁1，孔德澎1，郑玉珠1，沈毅韵2

单位：1.上海市宝山区仁和医院，上海 200431； 2.上海中医药大学附属宝山医院，上海 201999

引用：引用：顾静雯，傅伟，顾昳衡，董晨洁，孔德澎，郑玉珠，沈毅韵.平喘方通过外泌体miR-21-5p调控TGF-β/Smad2/3信号通路对哮喘小鼠气道重塑的保护作用[J].中医药导报,2026,32(5):49-54.

DOI：10.13862/j.cn43-1446/r.2026.05.008

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摘要：

目的：探讨平喘方对哮喘小鼠气道重塑的治疗作用及其潜在机制。方法：将40只6~8周龄的雄性BALB/c小鼠根据体质量随机分成空白组、哮喘模型组、平喘方治疗组和地塞米松治疗组，每组10只。除正常组外，其余3组均通过腹腔注射卵白蛋白（OVA）与铝镁佐剂混合物（20 μg/mL）的方式建立哮喘小鼠模型。平喘方治疗组小鼠从第15天开始每日灌胃给药0.2 mL；地塞米松治疗组小鼠则在相同时间段内灌胃地塞米松[0.75 mg/（kg·d）]；空白组小鼠灌胃生理盐水。持续28 d。给药完成后，通过HE染色、Masson染色、免疫组化、实时荧光定量PCR（qRT-PCR）和酶联免疫吸附试验（ELISA）等方法，检测小鼠肺组织病理学变化、气道重塑相关指标、外泌体miR-21-5p表达及转化生长因子-β（TGF-β）/Smad信号通路的变化。结果：与空白组比较，哮喘模型组小鼠出现显著气道炎症、平滑肌增厚、胶原沉积及上皮间质转化（E-cad表达下降、N-cad表达上升），且其外泌体miR-21-5p和肺组织TGF-β、p-Smad2/3表达显著上调，而Smad7表达显著下调。平喘方治疗组与哮喘模型组比较，上述病理变化均得到明显改善，并能显著下调miR-21-5p、TGF-β、p-Smad2/3的表达，同时上调Smad7的表达，差异均有统计学意义（P＜0.05）。平喘方治疗组在改善气道重塑、抑制纤维化及调节该信号通路的关键分子方面，效果与地塞米松治疗组相当，两组间差异不明显（P＞0.05）。结论：平喘方具有显著的抗哮喘作用，其机制可能与下调外泌体miR-21-5p，抑制TGF-β/Smad2/3信号通路，从而改善气道重塑有关。

关键词：哮喘；平喘方；地塞米松；气道重塑；外泌体；miR-21-5p；转化生长因子β/Smad信号通路；小鼠

Abstract：

Objective: To investigate the therapeutic effect of Pingchuan formula (PCF) on airway remodeling in a murine model of asthma and to elucidate its underlying mechanisms. Methods: Totally 40 male BALB/c mice (6-8 weeks old) were randomly divided into four groups based on body weight (n=10 per group): a blank group, an asthma model group, a PCF-treated group, and a dexamethasone (DEX)-treated group. Asthma was induced in the latter three groups by intraperitoneal injection of a mixture of ovalbumin (OVA) and aluminum-magnesium adjuvant (20 μg/mL). Starting on day 15th, the PCF-treated group received a daily oral gavage of PCF (0.2 mL), while the DEX-treated group received dexamethasone [0.75 mg/(kg·d)] as a positive control over the same period. The blank group received equivalent volumes of physiological saline without any sensitization. Each group was administered for 28 days. After treatment completion, pathological changes in lung tissue, airway remodeling-related indicators, exosomal miR-21-5p expression, and changes in the TGF-β/Smad signaling pathway were detected using methods including HE staining, Masson staining, immunohistochemistry, qRT-PCR, and enzyme linked immunosorbent assay (ELISA) respectively. Results: Compared to the blank group, the asthma model group exhibited marked airway inflammation, bronchial smooth muscle thickening, collagen deposition, and features of epithelial-mesenchymal transition (EMT), evidenced by decreased E-cadherin and increased N-cadherin expression. Furthermore, the asthma model group demonstrated a significant upregulation of exosomal miR-21-5p and pulmonary expression of TGF-β and phosphorylated Smad2/3 (p-Smad2/3), alongside a downregulation of Smad7. These pathological alterations were reversed in PCF-treated group compared to the asthma model group, leading to a notable downregulation of miR-21-5p, TGF-β, and p-Smad2/3 expression, and an upregulation of Smad7 (P＜0.05). The efficacy of PCF-treated group in mitigating airway remodeling, inhibiting fibrosis and modulating the key molecules of this pathway was comparable to that of DEX-treated group, with no statistically significant differences observed between the two groups (P＜0.05). Conclusion: Pingchuan formula has a significant anti-asthma effect. Its mechanism may be related to the downregulation of exosomal miR-21-5p and the inhibition of the TGF-β/Smad2/3 signaling pathway, thereby improving airway remodeling.

Key words：asthma; Pingchuan formula; dexamethasone; airway remodeling; exosomes; miR-21-5p; transforming growth factor β/Smad signaling pathway; mouse

发布时间：2026-05-23

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