目的 探究五味沙棘散对卵清蛋白（ovalbumin，OVA）诱导的过敏性哮喘大鼠的保护作用及机制。方法 SD大鼠随机分为对照组、模型组、地塞米松（0.5 mg/kg）组和五味沙棘散（0.5、2.0 g/kg）组，建立OVA诱导的大鼠早期支气管哮喘模型，苏木素-伊红（HE）和Masson染色观察支气管病理情况及纤维化程度；免疫组化检测支气管间隙连接蛋白43（connexin 43，Cx43）的表达和分布；ELISA检测血清中免疫球蛋白E（immunoglobulin E，IgE）和白细胞介素-13（interleukin-13，IL-13）水平；亚甲基蓝法和WSP-1荧光探针法测定血清中硫化氢（hydrogen sulfide，H₂S）水平。建立CdCl₂诱导的支气管上皮BEAS-2B细胞损伤模型，MTT法检测细胞活性；Hoechest 33342染色法观察细胞核形态变化；MitoSOX染色检测细胞线粒体活性氧（mitochondrial reactive oxygen species，mtROS）水平；Western blotting检测半胱氨酸天冬氨酸蛋白酶-3（cystein-asparate protease-3，Caspase-3）、核因子红细胞系2相关因子（nuclear factor erythroid 2-related factor，Nrf2）和Kelch样ECH关联蛋白1（Kelch like ECH associated protein 1，Keap1）蛋白表达。结果 五味沙棘散能够减少支气管黏膜上皮细胞脱落和黏液分泌（P＜0.001），降低胶原纤维的沉积和Cx43的表达及分布（P＜0.05、0.01、0.001），降低血清中IgE、IL-13水平（P＜0.05），升高血清中H₂S水平（P＜0.05、0.01）。五味沙棘散含药血清呈剂量相关性地抑制CdCl₂诱导的BEAS-2B细胞凋亡及mtROS水平（P＜0.01、0.001），上调Caspase-3和Nrf2蛋白表达（P＜0.05、0.01），下调Keap1蛋白表达（P＜0.01）。结论 五味沙棘散对OVA诱导的哮喘大鼠和CdCl₂诱导的支气管上皮细胞凋亡均具有保护作用，其机制可能与调控Nrf2/Keap1信号通路有关。

Objective To investigate the protective effect and mechanism of Wuwei Shaji Powder (五味沙棘散, WSP) on ovalbumin (OVA)-induced allergic bronchial asthma in rats. Methods SD rats were randomly divided into control group, model group, dexamethasone (0.5 mg/kg) group and WSP (0.5, 2.0 g/kg) groups, rats were sensitized with OVA to induce an early bronchial asthma model. Hematoxylin-eosin (HE) and Masson staining were used to observe the pathological changes and degree of fibrosis in the bronchi; Immunohistochemistry was performed to detect the expression and distribution of of connexin 43 (Cx43) in bronchi; ELISA was used to measure the levels of immunoglobulin E (IgE) and interleukin-13 (IL-13) in serum; Methylene blue method and WSP-1 fluorescence probe method were used to determine hydrogen sulfide (H₂S) level in serum. The CdCl₂-induced bronchial epithelial cell (BEAS-2B) injury model was established, cell viability was detected by MTT assay; Nuclear morphological changes were observed by Hoechest 33342 staining; Mitochondrial reactive oxygen species (mtROS) level in cell was detected using MitoSOX staining. The expression levels of cystein-asparate protease-3 (Caspase-3), nuclear factor erythroid 2-related factor (Nrf2) and Kelch like ECH associated protein 1 (Keap1) were analyzed by Western blotting. Results WSP could reduce the shedding of bronchial mucosal epithelial cells and mucus secretion (P < 0.001), decrease the deposition of collagen fibers and the expression and distribution of Cx43 (P < 0.05, 0.01, 0.001), lower the levels of IgE and IL-13 in serum (P < 0.05), elevated H₂S level in serum (P < 0.05, 0.01). WSP drug-containing serum showed dose-dependent inhibition of CdCl₂-induced BEAS-2B cell apoptosis and mtROS levels (P < 0.01, 0.001), up-regulation of Caspase-3 and Nrf2 protein expressions (P < 0.05, 0.01), and down-regulation of Keap1 protein expression (P < 0.01). Conclusion WSP has a protective effect on OVA-induced asthma rats and CdCl₂-induced apoptosis of bronchial epithelial cells, and its mechanism may be related to the regulation of Nrf2/Keap1 signaling pathway.

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中央本级重大增减支项目“名贵中药资源可持续利用能力建设项目”（2060302）；陕西省技术创新引导专项（基金）（2018HJCG-21）；陕西省科技厅一般项目（2021SF-368）；陕西省教育厅协同创新项目（21JY012）