1,25二羟维生素D3对哮喘小鼠的Rac1-IL33-ILC2通路的作用

The effect of 1,25-dihydroxyvitamin D3 on Rac1-IL33-ILC2 pathway in asthmatic mice

目的观察1,25二羟维生素D31,25-(OH)2-D3对哮喘小鼠Ras相关的C3肉毒素底物1(Ras-related C3 botulinum toxin substrate 1,Rac1)、白细胞介素-33(IL-33)和2型固有淋巴细胞(type 2 innate lymphocytes,ILC2)的影响。方法将30只7周龄BALB/c雌性小鼠随机分为对照组、哮喘组、干预组,每组各10只小鼠,卵清蛋白混合液致敏并雾化吸入建立哮喘小鼠模型,干预组每次激发前腹腔注射1,25(OH)2-D3混合液0.08 ml,对照组和哮喘组以生理盐水代替。末次激发24 h后对小鼠肺组织中IL-33、Rac1、ILC2进行检测并比较。结果与对照组比较,哮喘组Rac1下降,IL-33水平增高,ILC2数目升高。且Rac1与IL-33、ILC2呈明显的负相关性(r=-0.954、r=-0.957,P<0.05)。干预组IL-33及ILC2数目较哮喘组显著下降,Rac1较哮喘组显著上升,差异有统计学意义(P<0.05)。结论哮喘小鼠存在Rac1下降,IL-33水平增高,ILC2数目升高的免疫变化;1,25-(OH)2-D3可能通过上调哮喘小鼠Rac1的表达,导致IL-33等细胞因子水平产生减少,进而抑制ILC2的活化、减轻哮喘的免疫炎症。

Objective To observe the effects of 1,25-dihydroxyvitamin D3 on Ras-related C3 botulinum toxin substrate 1(Rac1),interleukin 33(IL-33)and type 2 innate lymphocytes(ILC2)in asthmatic mice.Methods We randomly divided 30 BALB/c female mice of 7-week-old into control,asthma and intervention groups,10 in each group.The mouse model of asthma was established by sensitization and aerosol inhalation of ovalbumin mixture.The intervention group was given intraperitoneal injection of 1,25-dihydroxyvitamin D3 mixture of 0.08 ml before each challenge,and the control group and asthma group were replaced with normal saline.IL-33,Rac1 and ILC2 in lung tissue of mice were detected after 24 hours of the last challenge.Results Compared with the control group,the level of Rac1 was decreased while the level of IL-33 and the number of ILC2 were increased in the asthma group.There was a significant negative correlation between Rac1 and IL-33 and ILC2(r=-0.954、r=-0.957,P<0.05).The number of IL-33 and ILC2 in the intervention group was significantly lower than that in asthma group while Rac1 in the intervention group was significantly higher than that in the asthma group.Conclusion There are immune changes in asthmatic mice with a decrease of Rac1,an increase of IL-33 level and an increase of ILC2 number.1,25-(OH)2-D3 may up-regulate the expression of Rac1 in asthmatic mice,resulting in the decrease of IL-33 and other cytokines,and then inhibit the activation of ILC2 and reduce the immune inflammation of asthma.