罗氟司特对变应性鼻炎小鼠Th17细胞因子IL-17表达的作用研究

Effect of roflumilast on intracellular expression of Th17 cytokine interleukin17in murine model of allergic rhinitis

目的：探讨罗氟司特对变应性鼻炎小鼠鼻组织中Th17细胞因子IL-17的作用与其机制。方法：6～8周BALB/C雌性小鼠36只随机分成模型组、治疗组、对照组，每组12只。利用卵清蛋白（ovalbumin,OVA）致敏模型组和治疗组小鼠建立变应性鼻炎模型，造模成功后模型组继续以OVA滴鼻，而治疗组在滴鼻前30min给予罗氟司特灌胃干预。对照组均以生理盐水代替。取鼻腔固定脱钙HE染色观察其病理变化，取鼻黏膜分别提取孤独核受体（retinoid-related orphan receptor, ROR）γt、IL-17及其RNA行western blot和RT-PCR，检测RORγt与IL-17蛋白和RNA水平的表达变化。结果：治疗组鼻部炎症浸润稍减轻，RORγt、IL-17表达相比模型组明显减轻，但仍高于对照组（P〈0.05）。结论：变应性鼻炎小鼠IL-17表达明显增高，说明IL-17对变应性鼻炎发病起着促进作用，同时发现罗氟司特能抑制鼻组织RORγt的表达，阻止Th17的分化，从而减少IL-17的分泌。

OBJECTIVE To study the effects of roflumilast on intracellular expression of Th17 cytokine interleukin 17 in mu- fine model of allergic rhinitis. METHODS 36 female BALB/C mice were divided into 3 groups： control group, allergic rhinitis （AR） group and treatment group. The allergic rhinitis models were induced by classical method with OVA. The treatment group was given with roflumilast. After last challenge, the pathological differences between the three groups were be surveyed. The levels of RORγt and IL-17 were measured by Western blot and reverse transcription-polymerase chain reaction（RT-PCR）. RESULTS The expressions of RORγt and IL-17 in treatment group were significantly lower than those of allergic rhinitis group, but significant higher than those of control group（P〈0. 05）. CONCLUSION The levels of IL-17 were highly increased in allergic rhinitis group, which might be associated with pathogenesis of allergic rhinitis. And it was also found that roflumilast could in- hibit the release of IL-17 probably by inhibiting RORγt expression and blocking Th17 differentiation in murine of allergic rhinitis.