Th1相关细胞因子及金黄色葡萄球菌定植诱导特应性皮炎大鼠炎症加剧

Th1 related cytokines and Staphylococcus aureus colonization induce inflammation aggravation in atopic dermatitis rats

目的探讨颗粒物(PM)形成的有机化合物乙二醛加重特应性皮炎(AD)症状的分子机制。方法选择40只雄性SD幼鼠为实验对象,于出生后第21天断奶,通过内皮下注射辣椒素构建AD模型,利用乙二醛蒸汽循环装置对幼鼠进行乙二醛干预。根据实验要求,将40小鼠随机分为乙二醛AD组(Gly-AD组)、单纯AD组(AirAD组)、单纯乙二醛组(Gly-naive组)和对照组(Air-naive组)。每周定期检测皮肤瘙痒和皮炎症状。采集大鼠皮肤和血液,分析金黄色葡萄球菌皮肤定植、抗菌肽和免疫球蛋白产生、炎性细胞因子mRNA表达等免疫学特征。结果①乙二醛可加重AD大鼠的瘙痒和皮炎,但未引起幼鼠的任何症状。②免疫荧光染色显示,AD大鼠皮肤表皮层中LL-37和β-defensin-2的表达显著高于幼鼠。与金葡菌定植结果相似,暴露于乙二醛后,AD和幼鼠表皮中LL-37和β-防御素-2的表达也明显升高。这表明抗菌肽表达的变化与乙二醛对金葡菌定植的增加有关。③乙二醛暴露后,AD大鼠TNF-α和IFN-γmRNA表达显著升高,而幼鼠TNF-α和IFN-γmRNA表达增加不明显。同时,暴露于乙二醛对AD和幼鼠IL-4和IL-5 mRNA的表达没有明显影响。且无论是AD大鼠还是幼鼠,暴露于乙二醛后血清IgG2b及IgE水平均保持不变。这表明,暴露于乙二醛可上调AD大鼠皮肤中的Th1免疫反应,而对Th2免疫反应无明显影响。结论在AD大鼠中,暴露于乙二醛加剧了皮肤瘙痒和炎症,这与金黄色葡萄球菌在皮肤的定植增加和Th1型免疫反应有关。

Objective To investigate the molecular mechanism of the aggravation of AD symptoms by glyoxal,an organic compound formed by PM.Methods Young rats and AD rats were exposed to fresh air and evaporative glyoxal for 5 weeks(2 h/d and 5 d/W),respectively. The symptoms of pruritus and dermatitis were detected regularly every week. Skin andblood samples were collected to analyze the immunological characteristics of Staphylococcus aureus(S. aureus)colonizationand inflammatory cytokines expression.Results(1)Glyoxal could aggravate the pruritus and dermatitis of AD rats,but didnot cause any symptoms of young rats.(2)The expression of LL-37 and β-defensin-2 in the epidermis of AD rats was signifi-cantly higher than that of young rats. Similar to the results of S. aureus colonization,the expressions of LL-37 and β-defensin-2 in AD and immature mouse epidermis were significantly increased after exposure to glyoxal.(3)After glyoxal exposure,the expression of TNF-α and IFN-γ m RNA in AD rats was significantly increased,while that of young rats was not. At thesame time,glyoxal exposure had no significant effect on the expression of IL-4 and IL-5 m RNA in AD and young rats. SerumIg G2 b and Ig E levels remained unchanged in AD rats and young rats after exposure to glyoxal.Conclusion In AD rats,gly-oxal exposure aggravates skin itching and inflammation,which is related to the increased colonization of Staphylococcus aureus and Th1 type immune response.