血必净对OVA诱导变应性鼻炎小鼠的干预作用及其对HO-1的影响

Anti-allergic effects of Xuebijing and potential role of heme oxygenase-1against ovalbumin-induced murine allergic rhinitis model

目的:研究血必净在OVA诱导的小鼠变应性鼻炎(AR)模型中的干预作用及其对血红素加氧酶-1(HO-1)表达的影响,探讨血必净注射液气道局部雾化吸入给药的可行性。方法:建立OVA诱导的小鼠AR模型,用血必净[1ml/(kg·d)]和地塞米松[30mg/(kg·d)]分别进行气道雾化治疗,对照组用PBS(pH 7.4)代替;检测各组小鼠鼻腔灌洗液中嗜酸粒细胞计数;ELISA法检测鼻腔灌洗液中炎性因子、OVA特异性IgE的表达水平;苏木精-伊红染色法检测鼻黏膜及肺组织的形态学变化;用Western Blot、Real-time PCR及免疫组织化学检测鼻黏膜及肺组织中HO-1的表达。结果:经血必净气道局部雾化吸入给药处理的小鼠可明显降低气道中的嗜酸粒细胞、炎性因子IL-4、IL-5、IL-13和TNF-α的表达水平,提高IFN-γ的表达水平;降低鼻腔灌洗液中OVA特异性IgE的表达水平;减少鼻黏膜和肺组织中黏液产生和炎症细胞的浸润;诱导鼻黏膜及肺组织HO-1的表达。结论:血必净注射液气道局部雾化吸入给药可以抑制OVA诱导的小鼠AR模型中炎性因子产生,逆转Th1/Th2失衡,其治疗作用可能与诱导鼻黏膜组织HO-1的高表达有关。

Objective： In this study, we investigated the anti-inflammation effects of Xuebijing in OVA-induced murine allergic rhinitis model. Furthermore, we determined whether heme oxygenase（HO）-i is required for the protective activity of Xuebijing. Method： Airways of OVA-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. Levels of interleukin IL-4, IL-5, IL-13, and tumor necrosis factor（TNF）-alpha in nasal lavage fluid were measured using enzyme-linked immunosorbent assays （EL1SAs）. Lung tissue and nasal mucosa sections were stained with Mayer＇s hematoxylin and eosin for assessment of cell infiltration and mucus production, Immunohistochemistry, Real-time PCR and Western Blot analyses for HO-1 protein expression. Result：Orally administered Xuebijing significantly inhibited the number of OVA-induced inflammatory cells and IgE production, along with reduced T-helper（Th）2 cytokine levels, such as IL-4, IL-5 and IL-13, improved the level of IFN-T, in nasal lavage fluid. In addition, Xuebijing induced a marked decrease in OVA induced inflammatory cell infiltration and mucus production in nasal and lung tissues. These effects were correlated with HO-1 mRNA and protein induction. Conclusion ： Our results indicate that Xuebijing protects against OVA-induced airway inflammation, at least in part, via HO-1 upregulation.