1,25-二羟维生素D3对哮喘大鼠调节性T淋巴细胞和气道炎症的影响

目的探讨1,25-二羟维生素D3[1,25(OH)2D3]对哮喘大鼠调节性T淋巴细胞(即CD4 CD25 Foxp3 T细胞)及气道炎症的影响。方法28只Wistar大鼠用卵白蛋白作为致敏原制备大鼠哮喘模型,然后随机分为四组(n=7)。治疗组1于激发前1 h给予口服1,25(OH)2D3;治疗组2于激发前1 h给予皮下注射地塞米松;治疗组3则于激发前1 h给予以上两药联合应用;组4于激发前1 h不用药(哮喘对照组)。分别测定各组大鼠支气管肺泡灌洗液(BALF)中IL-4和IL-10水平,计数总细胞数和嗜酸性粒细胞数;流式细胞仪检测外周血和脾脏单个核细胞中Treg与CD4 T细胞的比值;检测肺组织中IL-10和Foxp3mRNA表达。以未造模Wistar大鼠作为正常对照组(n=7)。结果哮喘对照组与正常对照组比较各项指标均有显著差异。与哮喘对照组比较,各哮喘治疗组大鼠BALF中细胞总数及嗜酸性粒细胞计数明显减少,IL-4水平降低而IL-10水平增高;外周血和脾脏单个核细胞中Treg与CD4 T细胞比值明显增高;肺组织中IL-10 mRNA和Foxp3 mRNA表达增加。各哮喘治疗组间及其与正常对照组间各项检测指标比较均无显著差异。结论哮喘大鼠给予1,25(OH)2D3可增加外周血和脾脏Treg比例和Foxp3mRNA表达水平。提示1,25(OH)2D3对Treg具有调节作用,对哮喘可能有潜在的治疗作用。

Effects of 1, 25-dihydroxyvitamin D3 on regulatory T cells and airway inflammation in asthmatic rats

Objective To investigate the effects of 1,25-dihydroxyvitamin D3[1,25(OH)2D3] on regulatory T cells(CD4 CD25 Foxp3 T cell)and airway inflammation in asthmatic rats. Methods Asthmatic models were established in 28 rats with ovalbumin as sensitinogen,and four groups were randomly divided(n=7).1,25(OH)2D3 was orally administered 1 h before challenge in treatment group 1,dexamethasone was subcutaneously injected 1 h before challenge in treatment group 2,both 1,25(OH)2D3 and dexamethasone were given 1 h before challenge in treatment group 3,while no medicine was administered 1 h before challenge in group 4(asthmatic control group).The levels of IL-4 and IL-10 in bronchoalveolar lavage fluid(BALF) were detected,the total cell numbers were obtained and the eosinophil count was performed.The ratios of Treg to CD4 T cells in peripheral blood and spleen mononuclear cells were measured with flow cytometry,and the mRNA expression of IL-10 and Foxp3 in lung tissues was detected.Wistar rats without asthma were served as normal controls(n=7). Results There were significant differences between asthmatic control group and normal control group in each parameter.Compared with asthmatic control group,the total cell number and eosinophil count decreased,the level of IL-4 decreased and the level of IL-10 increased in BALF in treatment groups.The ratios of Treg to CD4 T cells in peripheral blood and spleen mononuclear cells significantly increased,and the mRNA expression of IL-10 and Foxp3 in lung tissues increased in treatment groups compared with asthmatic control group.There was no significant difference between treatment groups and normal control group in each parameter. Conclusion Administration of 1,25(OH)2D3 increases the proportion of Treg and expression of Foxp3 mRNA in peripheral blood and spleen in asthmatic rats.1,25(OH)2D3 has a regulatory effect on Treg,and may serve as a potential therapeutic approach against asthma.