目的 探究草麻黄Ephedra sinica中一种鞣质化合物2β, 3β-epoxyfavan-5, 7, 4′-triol-(4α→8)-epiafzelechin（Ete）对卵清白蛋白（ovalbumin，OVA）致敏哮喘小鼠的干预作用，为丰富麻黄抗哮喘的研究以及拓展麻黄临床应用提供实验依据。方法SPF级雌性BALB/c小鼠适应性喂养1周，随机分为对照组、模型组、阳性对照药孟鲁司特钠（1.314 mg/kg）组和Ete低、高剂量（10、20 mg/kg）组，采用ip OVA与Al₂(OH)₃混悬液联合OVA雾化激发的方法建立哮喘小鼠模型，持续给药1周。通过检测小鼠咳嗽和喘息次数、气道高反应性、血清免疫球蛋白E（immunoglobulin E，IgE）以及小鼠肺部组织病理变化初步评价Ete抗OVA致敏哮喘的药效；多指标流式联合分析系统检测与哮喘密切相关的因子水平；流式细胞术检测小鼠肺组织活性氧、凋亡和钙离子水平以及小鼠机体免疫细胞（树突状细胞、嗜酸性粒细胞和肥大细胞）水平；ELISA检测小鼠血清白三烯C4（leukotrienes C4，LTC4）、组胺（histamine，HIS）、β-肥大细胞类胰蛋白酶（β-mast cell tryptase，MCT-β）水平；Western blotting检测肺组织中转化生长因子-β1（transforming growth factor-β1，TGF-β1）、Smad3、MUC5AC和表皮生长因子受体（epidermal growth factor receptor，EGFR）蛋白表达水平。结果 与模型组比较，Ete显著抑制哮喘小鼠气道高反应性，降低血清IgE水平（P＜0.01），减少咳、喘次数，延长咳、喘潜伏时间（P＜0.05、0.01），降低血清中IL-13、TNF-α、CCL11水平（P＜0.05、0.01），升高IL-10水平（P＜0.05），降低肺组织中活性氧、凋亡、树突状细胞和嗜酸性粒细胞水平（P＜0.05、0.01），降低肥大细胞及其脱颗粒过程关键介质LTC4、HIS、MCT-β和MCP-1的水平（P＜0.05、0.01），降低黏液分泌相关蛋白TGF-β1、Smad3、EGFR和MUC5AC的水平（P＜0.05、0.01）。结论 草麻黄中一种鞣质化合物Ete通过抑制肥大细胞活化和黏液蛋白分泌来改善OVA诱导的小鼠过敏性哮喘。

Objective To explore the intervention effect of a tannin compound 2β, 3β-epoxyfavan-5, 7, 4′-triol-(4α→8)-epiafzelechin (Ete), extracted from Ephedra sinica on ovalbumin (OVA)-sensitized asthmatic mice, providing experimental evidence to enrich the research on anti-asthmatic properties of Mahuang (Ephedrae Herba) and expand its clinical applications. Methods SPF female BALB/c mice were acclimatized for one week and randomly divided into control group, model group, positive drug montelukast (1.314 mg/kg) group and Ete low-, high dose (10, 20 mg/kg) groups. An asthma mouse model was established by intraperitoneal injection of OVA and Al₂(OH)₃ suspension combined with OVA atomization excitation, with continued administration for one week. The efficacy of Ete against OVA-sensitized asthma was evaluated by detecting cough and wheezing numbers, airway hyperresponsiveness, serum immunoglobulin E (IgE) and pathological changes of lung tissue in mice. Multi index flow based joint analysis system was used to detect the levels of factors closely related to asthma. Flow cytometry was used to detect the levels of reactive oxygen species (ROS), apoptosis and Ca²⁺ in lung tissue of mice and the levels of immune cells (dendritic cells, eosinophils and mast cells) in mice. The levels of serum leukotrienes C4 (LTC4), histamine (HIS) and β-mast cell tryptase (MCT-β) in mice were detected by ELISA. The protein expression levels of transforming growth factor-β1 (TGF-β1), Smad3, MUC5AC and epidermal growth factor receptor (EGFR) in lung tissue were detected by Western blotting. Results Compared with model group, Ete significantly inhibited airway hyperreactivity in asthmatic mice, reduced serum IgE level (P < 0.01), decreased the frequency of coughing and wheezing, and prolonged the latency for coughing and wheezing (P < 0.05, 0.01), lowered serum IL-13, TNF-α and CCL11 levels (P < 0.05, 0.01), while increased IL-10 level (P < 0.05), reduced levels of ROS, apoptosis, dendritic cells and eosinophils in lung tissue (P < 0.05, 0.01), decreased the levels of mast cells and key mediators involved in their degranulation process (LTC4, HIS, MCT-β and MCP-1) (P < 0.05, 0.01), reduced the levels of mucin-secreting proteins TGF-β1, Smad3, EGFR and MUC5AC (P < 0.05, 0.01). Conclusion A tannin compound Ete from E. sinica improves OVA-induced allergic asthma in mice by inhibiting mast cell activation and mucin secretion.

R285.5

国家重点研发计划—中医药现代化研究专项（2019YFC1708802）；国家自然科学基金资助项目（32200322）；河南省高层次人才特殊支持计划“中原千人计划”—中原领军人才（ZYQR201810080）；河南省科技研发计划联合基金（242301420082）