摘要
目的:研究IL-12真核表达质粒(psIL-12)在气道内表达对成年小鼠气道变态反应炎症的影响.方法:以卵白蛋白(OVA)复制成年小鼠气道变态反应炎症模型,气道内应用单剂量psIL-12,pcDNA3.1(+),PBS/脂质体复合物,同时设正常对照组.分别检测肺单链IL-12表达,计数支气管肺泡灌注液(BALF)中嗜酸粒细胞的百分比和IL-4,IFN-γ含量,观察肺组织形态学变化.结果:气道转染psIL-12可在小鼠肺组织中表达IL-12 mRNA;psIL-12干预组BALF中嗜酸粒细胞百分比为(2.6±2.3)%,较PBS对照组(11.6±2.3)%明显降低,两组组间差异具有显著性(P＜0.05).psIL-12干预组BALF中IL-4含量为(103±53)ng/L,IFN-γ含量为(171±20)ng/L,而PBS对照组IL-4含量为(319±12)ng/L,IFN-γ含量为(77±36)ng/L,两组组间差异具有统计学意义(P＜0.05).psIL-12可明显阻止模型鼠肺组织病理改变,降低血清中OVA特异性IgE抗体含量.结论:psIL-12转染气道表达IL-12,增加Th1型细胞因子IFN-γ的产生,抑制抗原激发的Th2型细胞因子IL-4产生,降低血清中OVA特异性IgE抗体含量,能明显抑制气道变态反应性炎症,有望成为治疗变应性鼻炎和支气管哮喘的新方法.
Abstract
AIM: To observe the immunological effects of eukaryotic expression plasmid paIL-12 on airway allergic inflammation in an ovalbumin-induced (OVA) murine model. METHODS: BALB/c mice were randomized into 4 groups: psIL-12 group, pcDNA3.1(+)group, PBS/Lipofectin complexment group and the healthy control group. The pathological manifestations of the lungs, the expression of IL-12 mRNA in the lung tissues, the eosinophils count, the levels of IL-4, IFN-γ in broncho-alveolar fluid (BALF) and the level of OVA-specific IgE in serum were detected. RESULTS: It was observed that large numbers of eosinophils infiltrated the lung tissues in the pathological sections of PBS/Lipofectin complexment group, significantly higher than that in psIL-12 group. The IL-12 mRNA was positively expressed in psIL-12 group, but negatively expressed in the other groups. The percentage of eosinophil (2.6±2.3 ) %, the level of IL-4 (103±53) ng/L and the level of OVA-specific IgE in BALF of psIL-12 group decreased significantly compared with those in the control group(P ＜0.05), while the level of IFN-γ ( 171± 20) ng/L increased significantly(P＜0.05) in psIL-12 group. CONCLUSION: psIL-12 exerts some therapeutic effect through modulating the balance between TH1 and TFI2 immune response by increasing the level of IFN-γand decreasing IL-4 and specific IgE levels. It can be used as a novel treatment for allergic rhinitis and asthma.
基金项目
国家科技攻关项目(2004BA720A19-02)
NETL
NSTL
维普
万方数据