实验性矽肺大鼠肺组织中Th1/Th2型细胞因子的变化及意义

目的研究实验性矽肺大鼠在染尘后不同时间肺组织中Th1型细胞因子IFN-γ和Th2细胞因子IL-4的变化,初步探讨Th1/Th2型细胞因子与矽肺发病机制的关系。方法将30只健康雄性SD大鼠随机分为模型组18只、对照组12只。模型组以非暴露方式气管内一次性注入1 ml二氧化硅悬液（40 g·L^-1）建立大鼠矽肺模型,对照组气管内注入等量的灭菌生理盐水。分别在染尘后第1、7、14、21、28、35天各处死3只模型组和2只对照组大鼠,免疫组化SABC法观察肺组织中IFN-γ和IL-4的表达情况,用图像分析系统进行定量分析。结果与对照组相比,染尘后第1、7、14、21天,模型组大鼠肺组织中IFN-γ表达明显增强（P〈0.05）;IL-4的表达显著减少（P〈0.05）。染尘后第28、35天,模型组大鼠肺组织中IFN-γ表达与对照组没有显著性差异（P〉0.05）;而IL-4的表达量大量增加,明显高于对照组（P〈0.05）。结论矽肺发展早期以Th1型细胞因子发挥细胞免疫调节作用为主;后期Th2型细胞因子分泌增加,体液免疫增强。

Changes and significance of Th1/Th2 cytokines in lungs of experimental silicotic rat

Aim To investigate changes of Th1/Th2 cytokines in Lungs at different developmental stages of rat silicosis models and to study the relationships between Th1/Th2 cytokines and the pathogenesis of silicosis.Methods Thirty healthy male SD rats were randomly divided into the silica exposure group and the control group.One ml silica suspension(40 g·L-1) was administrated via intratracheal instillation once while equal amount of saline was instilled to the rats of control group.Animals were sacrificed at the 1st,7th,14th,21st,28th,and 35th day after instillation,and the samples of lung tissues were collected.The expression of IFN-γ and IL-4 was observed by use of immunohistochemistry method and quantitative analysis of protein expressions by image analysis system.Results In early stage of experiment(1,7,14,21 d),the levels of IFN-γ in lungs of silicotic rats obviously increased than those in control group(P<0.05),the levels of IL-4 significantly decreased(P<0.05).In later stage(28,35 d),the levels of IFN-γ in lungs of silicotic rats had no obvious difference with control group(P>0.05),and the levels of IL-4 were significantly increased(P<0.05).Conclusion In early stage of silicosis,cell-mediated immunity by Th1 cytokines was dominant.But humoral-immunity enhanced In later stage,Th2 cytokines were increasingly secreted and humoral-immunity enhanced.