摘要： 目的 探讨Rho激酶抑制剂法舒地尔对变应性鼻炎小鼠鼻黏膜中辅助性T细胞1（Th1）、辅助性T细胞2（Th2）、辅助性T细胞17（Th17）的相关细胞因子（IFN-γ、IL-4、IL-17）及调节性T细胞（Treg）的特异性转录因子Foxp3 mRNA表达水平的影响。方法 将C57小鼠随机分为AR组（变应性鼻炎小鼠未给予药物治疗，n=8）、法舒地尔组（变应性鼻炎小鼠给予法舒地尔治疗，n=8）、对照组（正常小鼠未给予药物治疗，n=8）。利用卵清蛋白（OVA）建立小鼠变应性鼻炎模型。小鼠鼻黏膜HE染色，比较3组小鼠呼吸区黏膜的形态结构。实时荧光定量PCR法检测每组小鼠鼻黏膜中IFN-γ mRNA、IL-4 mRNA、IL-17 mRNA及Treg的特异性核转录因子Foxp3 mRNA的表达水平。结果 与对照组比较，AR组IL-4 mRNA、IL-17 mRNA表达明显升高，IFN-γ mRNA、Foxp3 mRNA表达降低（均P < 0.05）。与AR组比较，法舒地尔组变应性鼻炎症状（喷嚏、流涕、抓搔鼻部）明显缓解，嗜酸性粒细胞浸润减少，黏膜水肿减轻。IL-4 mRNA表达明显降低，IFN-γ mRNA、Foxp3 mRNA、IL-17 mRNA表达明显升高（均P < 0.05）。结论 法舒地尔可抑制变应性鼻炎小鼠鼻黏膜炎症反应，改善鼻黏膜局部Th1/Th2、Th17/Treg的免疫失衡。

法舒地尔对变应性鼻炎小鼠鼻黏膜中Th1/Th2、Th17/Treg相关细胞因子的影响

张玉, 韩佳利

中国医科大学附属第一医院耳鼻咽喉科, 沈阳 110001

收稿日期:2019-07-02出版日期:2020-07-30发布日期:2020-07-02
通讯作者:韩佳利E-mail:jiali_han@163.com
作者简介:张玉(1994-),女,硕士研究生.
基金资助:国家自然科学基金（81100708）


关键词: 变应性鼻炎, 法舒地尔, 辅助性T细胞1, 辅助性T细胞2, 辅助性T细胞17, 调节性T细胞, 细胞因子
Abstract: Objective This study investigated the function of fasudil on the mRNA expression of IFN-γ,IL-4,IL-17,and Foxp3 related to Th1,Th2,Th17 and Treg in the nasal mucosa of mice with ovalbumin-induced allergic rhinitis (AR). Methods C57 mice were divided randomly across three groups:an AR group,a fasudil group,and a control group. The AR group mice were sensitized and challenged by ovalbumin (OVA) without treatment. The fasudil group mice were treated with fasudil using the same process as the AR group. The control group mice were normal controls treated with normal saline. The nasal mucosa of each group was stained with HE to observe the morphological and structural and compare the differences of the respiratory mucosa of the three groups. The mRNA expression levels of IFN-γ,IL-4,IL-17,and Foxp3 in the nasal mucosa of each group were detected using real-time fluorescence quantitative PCR. Results Compared with the control group,the mRNA expression of IL-4 and IL-17 were significantly higher in the AR group (P < 0.05), while the mRNA expression of IFN-γ and Foxp3 were significantly lower in the AR group (P < 0.05). Compared with the AR group,fasudil treatment significantly alleviated the symptoms of allergic rhinitis-such as sneezing,runny nose,itchy nose-and improved inflammation of the nasal mucosa in mice with AR by reducing the infiltration of eosinophils and alleviating mucosal edema. The fasudil group exhibited significantly decreased levels of IL-4 mRNA expression and increased levels of IFN-γ,Foxp3,and IL-17 mRNA expression (P < 0.05). Conclusion Fasudil inhibits mucosal inflammation associated with AR and improves the imbalance of Th1/Th2 and Th17/Treg in the nasal mucosa.
Key words: allergic rhinitis, fasudil, T helper cell 1, T helper cell 2, T helper cell 17, regulatory T cell, cytokine
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