重组鼠白细胞介素-12腺病毒载体对哮喘小鼠模型IL-4、IFN-γ表达的影响

Effects of recombinant adenovirus vector carrying murine IL-12 gene on expression ofIL-4 and IFN-γin asthma mouse models

目的探讨重组鼠白细胞介素-12(IL-12)基因的腺病毒载体(AdCMVIL-12)对小鼠支气管哮喘模型IL-4、IFN-γ表达的影响。方法雌性BALB/c小鼠50只,按数字随机表法分为5组,每组10只:哮喘模型组、AdCMVIL-12组、AdCMVLacZ组、激素治疗组和正常对照组。并于第20天分别鼻内吸入50μL生理盐水和5×108 PFU AdC-MVIL-12。第28天收集各组小鼠的支气管肺泡灌洗液(BALF),检测IL-4、IFN-γ的变化,RT-PCR方法检测各组肺组织中IL-4、IFN-γmRNA的表达水平。结果哮喘模型组与对照组、AdCMVIL-12组相比较,BALF中的IL-4表达水平明显升高,而IFN-γ在AdCMVIL-12组中的表达水平显著上升。RT-PCR结果显示,哮喘模型组小鼠肺组织IL-4mRNA的表达与AdCMVIL-12组、激素治疗组及正常对照组相比较明显升高;而IFN-γmRNA的表达水平明显下降。结论 AdCMVIL-12对哮喘小鼠的气道及肺组织内的IL-4表达有明显的抑制作用,其机制可能与AdCMVIL-12阻断IL-4的表达,调节Th1/Th2类细胞因子的平衡有关。

Objective To investigate the effects of recombinant adenovirus vector carrying murine interleukin-12 gene（AdCMVIL-12） on the expression of IL-4 and IFN-γ in murine asthma model.Methods 50 BALB/c female mice were randomly divided into 5 groups：asthma model,AdCMVIL-12,AdCMVLacZ,Pulmicort Respules and control.Asthma models were established in each group except normal control group,saline（50 μL） and 5×108 PFU AdCMVIL-12 were given by intranasal administration at the 20th days.BALF were collected at the 28th day for detect the levels of IL-4 and IFN-γ.The levels of lung tissue IL-4 and IFN-γmRNA in each groups were detected by RT-PCR.Results Compared with group normal control and AdCMVIL-12,the levels of BALF IL-4 increased significantly in group Asthma model.The levels of IFN-γ in group AdCMVIL-12 were increased obviously.RT-PCR showed the levels of IL-4 mRNA in lung tissue were signifantly elevated than group AdCMVIL-12,Pulmicort Respules and control,the levels of IFN-γ mRNA were obviously reduced.Conclusion AdCMVIL-12 can significantly inhibit the expression of IL-4 in airway and pulmonary tissue in asthma model,its mechanism may be related to IL-12 blocking the expression of IL-4 and regulating the balance of Th1/Th2 cytokines.