鼠白细胞介素12质粒对小鼠支气管哮喘模型气道炎症及细胞因子的影响

The effect of a mouse IL-12 plasmid on airway inflammation and cytokine production in a mouse asthmatic model

目的 研究鼠白细胞介素 12 (IL 12 )基因表达 (mIL 12 )质粒对小鼠支气管哮喘 (简称哮喘 )模型气道炎症及细胞因子的影响 ,并分析其作用机制。方法 卵白蛋白 (OVA)致敏建立小鼠哮喘模型。BALB/c小鼠 4 1只 ,分为 6组。即哮喘模型组 (A组 ) 8只 :OVA致敏 +OVA气雾攻击 ;模型对照组 (B组 ) 6只 :用生理盐水代替 1%OVA溶液雾化 ,余处理同A组 ;mIL 12质粒预防组 (C组 ) 8只 :实验第 1、3、5天各肌肉注射mIL 12质粒 10 0 μg ;mIL 12质粒治疗组 (D组 ) 8只 :实验第 14、16、18天各肌肉注射mIL 12质粒 10 0 μg ;空质粒预防组 (E组 ) 5只 :实验第 1、3、5天各肌肉注射空质粒 10 0 μg ;空质粒治疗组 (F组 ) 6只 :实验第 14、16、18天各肌肉注射空质粒 10 0 μg。测定所有小鼠支气管 肺泡灌洗液 (BALF)中的嗜酸粒细胞 (EOS)个数和IL 4、IL 5、γ干扰素 (IFN γ)水平。结果B组小鼠EOS个数和IL 4、IL 5、IFN γ浓度分别为 (0 0 1± 0 0 3)× 10 8/L、(2 4± 4 ) pg/ml、(33± 6 ) pg/ml、(72 5± 5 9) pg/ml,C组为 (0 0 6± 0 0 4 )× 10 8/L、(43± 13) pg/ml、(6 3± 10 )pg/ml、(6 2 6± 6 0 ) pg/ml,D组为 (0 11± 0 12 )× 10 8/L、(38± 14 )pg/ml、(6 6± 14 ) pg/ml、(6 6 1± 4 0 ) pg/ml,与A?

Objective To investigate the effect of a mouse IL-12 gene expressive plasmid (mIL-12 plasmid) on the airway inflammation and the cytokine production in asthmatic mice and to study the possible mechanisms. Methods A mouse model of asthma was established by sensitization with ovalbumin (OVA). Forty-one BALB/c mice were divided into six groups including an asthmatic model group (group A, eight mice, sensitized with OVA plus challenging with OVA by aerosol), a model control group (group B, six mice, sensitized with OVA plus aerosolizing with normal saline), a mIL-12 plasmid prevention group (group C, eight mice, receiving intramuscularly mIL-12 plasmid 100 μg on day 1, day 3, and day 5), a mIL-12 plasmid treatment group (group D, eight mice, receiving intramuscularly mIL-12 plasmid 100 μg on day 14, day 16, and day 18), an empty plasmid prevention group (group E, five mice, receiving intramuscularly empty plasmid 100 μg on day 1, day 3, and day 5), and an empty plasmid treatment group (group F, six mice, receiving intramuscularly empty plasmid 100μg on day 14, day 16 and day 18). The number of EOS and the concentration of IL-4, IL-5 and IFN-γ in the mouse bronchoalveolar lavage fluids (BALF) were detected. Results The number of EOS and the concentration of IL-4, IL-5 and IFN-γ from group B were (0.01±0.03)×10 8/L,(24±4)pg/ml,(33±6)pg/ml,(725±59)pg/ml,respectively; those from group C were (0.06±0.04)×10 8 /L,(43±13)pg/ml,(63±10)pg/ml,(626±60)pg/ml, respectively, and those from group D were (0.11±0.12)×10 8 /L,(38±14)pg/ml,(66±14)pg/ml, (661±40) pg/ml, respectively; the difference was significant as compared with those from group A [(2.97±1.20)×10 8/L, (122±45)pg/ml, (126±34)pg/ml, and (435±49)pg/ml] ( P <0.001). The number of EOS and the concentration of IL-4, IL-5 and IFN-γ from group C and group D also showed significant difference in comparison with those from group E [(1.96±0.93)×10 8/L, (110 ±24)pg/ml, (112±11)pg/ml and (464±51) pg/ml], and group F [(2.11±0.90)×10 8/L, (88±17)pg/ml, (107± 6)pg/ml and (481±64)pg/ml]( P <0.01). Conclusion The mIL-12 plasmid can significantly inhibit airway inflammation. Its regulatory effect on the balancing of Th1/Th2 cytokines may be a possible mechanism.