小鼠皮下感染着色芽生菌病皮损中局部细胞免疫功能研究  

The cell-mediated immune reaction in the cutaneous lesions of the muriue chromoblastomycosis

作　　者：王红[1] 魏欣净[1] 贾青[3] 沈永年[2] 吕桂霞[2] 刘维达[2] 

机构地区：[1]山东大学附属省立医院皮肤科,济南250021 [2]中国医学科学院皮肤病研究所,南京210042 [3]山东省医学科学院基础医学研究所试验病理室

出　　处：《中华微生物学和免疫学杂志》2010年第8期704-709,共6页Chinese Journal of Microbiology and Immunology

基　　金：公益性卫生行业科研专项基金（200802032）;国家科技重大专项：抗感染药物临床前药效评价技术与平台（抗真菌药效评价）（2009ZX09303-005）

摘　　要：目的 利用小鼠皮下着色芽生菌病模型,研究在不同的病程发展阶段其T细胞免疫功能的变化.方法 足垫局部皮下注射法建立小鼠的裴氏着色霉感染的着色芽生菌病模型,通过免疫组织化学技术,检测正常小鼠足垫皮肤皮损局部细胞因子IFN-γ、IL-4、IL-10、TNF-α的表达并作为对照组,观察免疫正常组和环磷酰胺免疫抑制处理的免疫抑制组小鼠分别在感染上述真菌后7 d、30 d时,皮损局部细胞因子水平变化,并与对照组比较.结果 在着色芽生菌病小鼠模型中,第7天时,免疫正常组IL-4、TNF-α和IL-10较正常对照组均出现了显著的升高（P＜0.01）,表现为Th1和Th2型细胞免疫均增强的模式,并以Th2型为主 30 d时IL-10表达显著下降（P＜0.01）,与同期正常对照组比较差异无统计学意义（P=0.52）,IFN-γ、TNF-α水平比7 d时显著升高（P＜0.01）,表现为Th2型细胞免疫减弱Th1型占主导的模式.免疫功能受损组第7天时IL-10、IL-4的水平升高与其他两组相比差异均有统计学意义（P＜0.01）,IFN-γ表达水平则明显下降（P＜0.01）,TNF-α的表达与正常对照组相比差异无统计学意义（P=0.39）,表现为Th2型细胞免疫增强Th1功能受抑模式 30 d时,IL-10表达水平较7 d时显著减少,但仍然高于同期的免疫正常组和正常对照组,IFN-γ、TNF-α水平显著升高（P＜0.01）,但却低于免疫正常组,表现为Th2型免疫模式渐弱Th1功能逐渐增强模式.结论 在不同免疫状态下小鼠着色芽生菌病感染的过程中,随着病情好转存在由Th2型细胞免疫为主导转化为Th1型细胞免疫功能占主导的过程,免疫抑制下主要表现为Th1反应受抑制,Th1型细胞因子在控制着色芽生菌病的发展过程中具有关键性的保护作用,Th2型细胞因子则可能与感染的发展进程相关.Objective To evaluate the cell-mediated immune tissue reactions of mice model of chromoblastomycosis. Methods First we developed a murine model of chromoblastomycosis subcutaneous infection with F. pedrosoi inoculated into the footpads using immunocompetent and immunocompromised mice immuned by CTX, and then by immunohistochemistry methods analyzed the expression of cytokines IL-4, IL-10, TNF-α and IFN-γ at the seventh and thirtieth day, the expression of these cytokines at the same time in the healthy mice footpads were used as control. Results In the immunocompetent mice, The expression of IL-4, IL-10 and TNF-α was significantly higher when compared with healthy control at the seventh day,showing an up-regulation pattern of Th2 and Th1 type cellular immune functions with a predominance of the Th2 response. At the 30th day, the expression of IL-10 was significantly lower when compared with the 7th day and no difference with healthy controls, while IFN-γand TNF-α were gradually increased, the T cellmediated immune drives to Th1 response from Th2. In the immunocompromised mice, the expression of IL4 and IL-10 were significantly higher, meanwhile IFN-γwas lower than those in immunocompetent or healty mice, the levels of TNF-α was not significantly different fiom healty control at the 7th day, it showed that Th2 response was more increased with the Th1 responses was significantly inhibited in the early immune reactions. At the 30th day, the Th1 type cytokines IFN-γ and TNF-α were highly significantly higher than early stage but still lower than immunocompetent levels, the level of Th2 type cytokine IL-10 rradually decreased although it was still above the other two rroups. Conclusion In different immune state, there was an immune defence translation from the predominance of Th2 type cellular immunity to Th1 type in the process of murine model of chromoblastomycosis. Thl type cytokines which favors resistance to fungal disease, played a major role at controlling the development of chromoblastomycosis.

关 键 词：着色芽生菌病 动物试验 细胞因子 Th2/Th1 

分 类 号：R756[医药卫生—皮肤病学与性病学]