IL-23在变应性鼻炎小鼠模型中的作用及机制的研究

Effect of IL-23 in a model of allergic rhinitis and its mechanism

目的:探讨IL-23在变应性鼻炎小鼠模型中的作用及机制的研究。方法:应用卵清蛋白(OVA)致敏建立小鼠变应性鼻炎模型,给予抗IL-23p19单克隆抗体干预,计量抗原激发后小鼠搔鼻数量。应用HE染色方法检测IL-23对小鼠鼻黏膜炎症影响,应用ELISA法检测小鼠灌洗液中IL-4、IFN-γ及IL-17A含量。应用PCR方法检测鼻黏膜中FOXP3的含量。结果:治疗后抗IL-23p19抗体组小鼠搔鼻症状相对于抗体对照组明显减轻(P<0.05),与PBS组比较,OVA组小鼠鼻黏膜炎症细胞浸润明显(P<0.01),鼻腔灌洗液中嗜酸性粒细胞数明显升高(P<0.05);抗IL-23p19抗体治疗后,小鼠鼻黏膜炎症细胞浸润显著降低(P<0.05),鼻腔灌洗液中嗜酸性粒细胞数明显降低(P<0.05);抗IL-23p19抗体治疗后,IL-4及IL-17A含量较IgG抗体对照组降低(P<0.05),IFN-γ含量不变(P>0.05)。抗IL-23p19抗体治疗后,FOXP3含量较IgG抗体对照组增高(P<0.05)。结论:抗IL-23p19抗体可有效治疗小鼠变应性鼻炎,其机制可能是抑制Th17细胞的增殖并且促进调节性T细胞的功能。

Objective： To explore the effect of IL-23 in the treatment of allergic rhinitis in mice. Methods： A model of allergic rhinitis was established with Ovalbumin（ OVA）,and then the mice were treated with anti-IL-23p19. The nasal rubs were counted. HE staining was performed and the number of total inflammatory cells and eosinophils was counted in the nasal lavage. The content of IL-4,IFN-γ and IL-17 A were measured by ELISA. The amount of FOXP3 in the local mucosa was measured by Real-time PCR method. Results： Compared to Ig G control group,after the treatment of anti-IL-23p19,the nasal rubs were decreased（ P0. 05）. Compared to PBS group,the total inflammatory cells in the nasal mucosa and NLF eosinophils showed significant difference for the OVA group（ P0. 01 and P 0. 05 respectively）,but after the anti-IL-23p19 treatment,they were significantly decreased（ P 0. 05）. IFN-γwas not different among different groups（ P0. 05）. But after the anti-IL23p19 treatment,the IL-4 and IL-17 A production was significantly decreased（ P0. 05）. Moreover,after the anti-IL23p19 treatment,the amount of local FOXP3 was significantly enhanced（ P 0. 05）. Conclusion： Anti-IL-23p19 treatment has a therapeutic effect on the allergic rhinitis of mice partly by limiting Th17 response and enhancing T regulatory response.