目的 探究欧前胡素对哮喘模型小鼠气道炎症的影响及其作用机制。方法 将50只雄性BALB/c小鼠随机分成5组，即对照组、模型组及欧前胡素低、中、高剂量（15、30、60 mg/kg）组。采用HE、Masson、PAS染色观察小鼠肺组织病理学改变；ELISA法检测小鼠肺泡灌洗液（BALF）中免疫球蛋白E（IgE）及白细胞介素-4（IL-4）、IL-5、IL-13、γ-干扰素（IFN-γ）水平；双氢罗丹明（DHR）-123法检测小鼠BALF中活性氧（ROS）的含量；检测小鼠肺组织中蛋白羰基含量及丙二醛（MDA）水平；抗氧化酶试剂盒检测小鼠BALF中超氧化物歧化酶（SOD）活性、谷胱甘肽（GSH）水平及总抗氧化能力（TAOC）；免疫组织化学法和Western blotting法检测小鼠肺组织中核因子E2相关因子2（Nrf2）及血红素氧合酶1（HO-1）蛋白表达水平。结果 与模型组比较，欧前胡素能够减少哮喘小鼠肺组织炎症细胞的渗出、杯状细胞的增生和胶原沉积；减少BALF中ROS、总IgE和卵清蛋白（OVA）特异性IgE的表达；降低IL-4、IL-5、IL-13、蛋白羰基、MDA的量并增加IFN-γ、SOD、GSH水平及TAOC；提高肺组织中Nrf2和HO-1蛋白表达水平。结论 欧前胡素对OVA诱导的哮喘模型小鼠具有治疗作用，其作用机制可能与Nrf2/HO-1通路活化有关。

Objective To explore the therapeutic effect of imperatorin (IMP) in the asthmatic mice model, and study whether its mechanism is related to Nrf2/HO-1 signaling pathway. Methods A total of 50 male BALB/c mice were randomly divided into five groups, namely the control group, the OVA asthma model group, and the IMP low, medium and high dose treatment groups (15, 30, and 60 mg/kg). HE, Masson, and PAS staining were used to observe lung histopathological changes in mice; ELISA was used to detect the contents of IL-4, IL-5, IL-13, IFN-γ, and IgE in the BALF of mice; DHR-123 was used to detect the content of ROS in the mice BALF; The expression levels of protein carbonyl and MDA in lung tissues of mice were measured; The anti-oxidant enzyme kit was used to detect SOD, GSH, and total antioxidant capacity (TAOC) in BALF; immunohistochemical method was used to detect the expression levels of Nrf2 and HO-1 in lung tissues; The contents of Nrf2 and HO-1 in lung tissues were quantitatively analyzed by Western blotting. Results Compared with the model group, IMP reduced the exudation of inflammatory cells, the proliferation of goblet cells, and collagen deposition; IMP reduced the expression of ROS, total IgE, and OVA specific IgE in BALF; IMP decreased the contents of IL-4, IL-5, IL-13, protein carbonyl, and MDA, and increased the content of IFN-γ, SOD, GSH, and TAOC; The results of immunohistochemistry indicated that IMP increased the expression of Nrf2 and HO-1 in lung tissues; Western blotting showed that IMP induced Nrf2 nuclear translocation and the expression of HO-1 at the protein level. Conclusion IMP plays a therapeutic role in asthmatic mice induced by OVA, and its mechanism may be related to the activation of Nrf2/HO-1 pathway.

国家自然科学基金资助项目（81660003，81560679）