全反式维甲酸对哮喘小鼠气道炎症及辅助性T细胞17/调节性T细胞功能的影响

摘要

Objective To investigate effect of all trans retinoic acid (at-RA) on airway inflammation and Th17/regulatory T cell (Treg) function in asthmatic mice.Methods Bronchial asthma mouse model was established by sensitazation with intraperitoneal injection and stimulation with aerosol inhalation.The mice were treated with at-RA and prednisone for 15 days(once per day),respectively.In addition to that,normal group and model group were established.Inflammation changes,cell counts and IL-17,IL-10 and TGF-β levels in bronchoalveolar lavage fluid(BALF)were observed in each group.Results Pulmonary inflammation was significantly allevated in prednisone group[7.5 mg/(kg · day)]and high dose at-RA group[10 mg/(kg · day)] as compared with model group.Inflammation of low dose at-RA group[5 mg/(kg · day)]was between that of modle group and prednisone group.Cell counts and IL-17,IL-10 and TGF-β levels in BALF were significantly higher in model group than in normal group.The cell count significantly descended in prednisone and high dose at-RA groups.Cell count also decreased in low dose at-RA group,but it was still higher than that in prednisone and high dose at-RA groups.In the model group and low dose at-RA group,the content of IL-17 was significantly increased while the content of IL-10 and TGF-β was significantly reduced as compared with the control group.And there was no significant difference between the prednisone group,high dose at-RA group,and normal group.Compared with the normal group,the content of IL-17 was significantly reduced while the content of IL-10 and TGF-β was significantly increased in prednisone group,high and low dose at-RA groups.There were no significant differences in cytokines between the prednisone group and high dose at-RA group.Compared with the prednisone group and high dose at-RA group,the content of IL-17 was significantly increased while the content of IL-10 and TGF-β was significantly reduced in low dose at-RA group.Conclusion At-RA can improve the airway inflammatory response of asthmatic mice by regulating the cellular function of Th17/Treg,thus providing new interventions for the treatment of bronchial asthma.%目的 研究全反式维甲酸对支气管哮喘小鼠气道炎症及辅助性T细胞17(Th17)/调节性T细胞(Treg)细胞功能的调节作用.方法 采用卵清蛋白(OVA)腹腔注射致敏和雾化吸入激发建立支气管哮喘小鼠模型,分别用全反式维甲酸及泼尼松干预治疗15 d(1次/d),同时设立正常组及模型组.观察各组小鼠肺组织的炎症改变、细胞计数及肺泡灌洗液中IL-17、IL-10及TGF-β的含量.结果 泼尼松[7.5 mg/(kg·d)]组及全反式维甲酸高剂量[10 mg/(kg·d)]组肺部炎症改变较模型组明显减轻,全反式维甲酸低剂量[5 mg/(kg·d)]组炎症反应介于模型组及泼尼松组之间.模型组肺泡灌洗液中细胞总数、嗜酸性粒细胞及中性粒细胞计数均明显高于正常组;经泼尼松及高剂量全反式维甲酸干预后,细胞计数均明显下降,维甲酸低剂量组也呈下降趋势.模型组及全反式维甲酸低剂量组IL-17含量明显高于正常组,IL-10及TGF-β含量均低于正常组;而泼尼松组及全反式维甲酸高剂量组与正常组之间差异无统计学意义.与模型组相比,泼尼松组及全反式维甲酸高、低剂量组IL-17含量明显降低,IL-10及TGF-β的含量升高.泼尼松组及全反式维甲酸高剂量组各细胞因子之间无明显差异;与全反式维甲酸高剂量及泼尼松组相比,全反式维甲酸低剂量组IL-17含量升高,而IL-10及TGF-β含量降低.结论 全反式维甲酸可以通过调节Th17/Treg的细胞功能,从而改善哮喘小鼠的气道炎症反应,为治疗支气管哮喘提供新的干预措施.