动态研究地塞米松对哮喘小鼠肺IL-25mRNA和IL-25表达的影响

Dynamic effect of dexamethasone on IL-25 mRNA and its expression in the lung tissue of asthmatic mice

目的哮喘的作用机制中经典细胞因子研究得较多,但一些非经典的细胞因子同样发挥一定的作用,如白细胞介素(interleukin,IL)-25。本实验拟初步研究IL-25mRNA和IL-25在支气管哮喘中的变化趋势及地塞米松对两者的作用,以进一步了解糖皮质激素在哮喘病治疗的作用机制。方法清洁级BALB/c小鼠随机分为正常组(分第1次致敏后、第2次致敏后、激发后),哮喘组(分第1次致敏后、第2次致敏后、激发后)和地塞米松组。以鸡卵清白蛋白(ovalbumin,OVA)致敏激发法建立哮喘模型。地塞米松组在每次激发前1h予地塞米松腹腔注射。正常组予等渗盐水致敏和激发。用ELISA法测定支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中IL-25水平;用Real-time PCR法检测肺组织IL-25mRNA相对含量。结果第1次致敏后IL-25和IL-25mRNA表达正常组较哮喘组增加(P<0.05),第2次致敏后两者表达哮喘组较正常组增加(P<0.05),激发后两者表达哮喘组较正常组增加(P<0.05);两者表达地塞米松组较哮喘组激发后减少(P<0.05),但IL-25表达高于正常组激发后(P<0.05),而IL-25mRNA表达无差异。结论 IL-25参与了哮喘病炎症前及炎症免疫发病的整个过程。糖皮质激素治疗哮喘病的机制之一,可能是抑制了IL-25的表达。

Objective While the action mechanisms of classic cytokines in asthma receive more attention from researchers, some non-classic cytokines, such as IL-25, also play a certain role. This study was to investigate the changes of IL-25mRNA and IL-25 （IL-17E） in bronchial asthma, and further understand the action mechanisms of glucocorticoids in asthma. Methods Clean grade BALB/c mice were randomly divided into three normal groups （ after the first and second sensitization and excitation） , three asthma groups （after the first and second sensitization and excitation） and a dexamethasone group. Asthma models were established by the ovalbumin-sensitized excitation method. The mice of the dexamethasone group were intraperitoneally injected with dexamethasone 1 hour before each excitation, while those of the normal groups were sensitized and excited with isotonic saline. The IL-25 level in the bronchoalveolar lavage fluid was measured by ELISA, and the relative content of IL-25mRNA in the lung tissue detected by real-time PCR. Results Compared with the asthma groups, both IL-25 and IL-25mRNA were significantly increased （P 〈 0.05 ）, but re markably decreased after the second sensitization （ P 〈 0.05 ） and excitation （ P 〈 0.05 ） in the normal groups. The dexamethasone group showed significantly lower levels of IL-25 and IL-25mRNA than the asthma group after excitation （P 〈 0.05 ） and a higher level of IL-25 than the normal group after excitation （ P 〈 0.05 ）, but there was no significant difference in the expression of IL-25mRNA be tween the dexamethasone and normal group after excitation. Conclusion IL-25 is involved in the whole process of inflammation andinflammatory immune pathogenesis of asthma. One of the mechanisms of giucocorticoid acting on asthma may be its inhibitory effect on the expression of IL-25.