变应原特异性免疫治疗对尘螨致敏的特应性皮炎小鼠疗效观察

Effects of Allergen Specific Immunotherapy on Dust Mite Sensitized Atopic Dermatitis-Like Mice

目的 观察尘螨致敏的特应性皮炎(atopic dermatitis, AD)样小鼠免疫学特征以及变应原特异性免疫治疗(allergen specific immunotherapy, ASIT)对该模型的疗效。方法 将BABL/c小鼠分为三组,对照组(Control)、特应性皮炎模型组(AD)、特应性皮炎脱敏治疗组(AD+ASIT)。用二硝基氟苯(dinitrofluorobenzene, DNFB)和尘螨提取物擦拭AD组及AD+ASIT组背部皮肤,进行炎症诱导,重复8周。第4周起另给予AD+ASIT组递增剂量的脱敏剂阿罗格进行治疗。取小鼠背部皮肤进行病理切片观察、收集淋巴结细胞,流式检测T细胞胞内炎症因子,ELISA方法检测外周血浆总IgE及皮肤、淋巴结中细胞因子含量。结果 AD组小鼠皮肤出现红斑、脱屑、水肿等现象,表皮明显增厚,淋巴结明显增大,嗜酸性粒细胞和肥大细胞大量浸润;淋巴结和皮肤IL-4含量增加。AD+ASIT脱敏治疗组小鼠较AD组皮损炎症减轻,嗜酸性粒细胞和肥大细胞浸润数量降低,淋巴结IL-4含量显著降低。结论 二硝基氟苯、尘螨反复刺激背部皮肤可诱导BABL/c小鼠产生以Th2型炎症反应为主的特应性皮炎样损害,以阿罗格进行皮下注射的脱敏治疗可改善该Th2炎症性皮损。本研究是对小鼠脱敏治疗模型的又一次探索和丰富,为后续脱敏治疗模型方案的选择提供了参考。

Objective To observe the immunological characteristics of atopic dermatitis-like mice sensitized by dust mite, and analyze the effects of allergen specific immunotherapy on this model.Methods BABL/c mice were divided into three groups, control group(Control), atopic dermatitis model group(AD), and group of atopic dermatitis with desensitization treatment(AD+ASIT). Backs of AD and AD+ASIT group mice were wiped with dinitrofluorobenzene(Dinitrofluorobenzene, DNFB) and dust mite extracts. The treatments were repeated for 8 weeks. From the 4 th week, the AD+ASIT group was given desensitization treatment with increasing dose. After that, mice were sacrificed, and the back skin was taken for pathological observation. Lymph node cells were collected for flow cytometry tests, and intracellular inflammatory factors of T cells were detected. Elisa kit was used to detect the total IgE content in peripheral plasma, and the cytokines in skin and lymph nodes were evaluated by liquid flow method.Results In AD group, erythema, desquamation, and edema appeared, epidermis thickened, the lymph nodes were enlarged, eosinophils and mast cells were infiltrated, concentration of IL-4 in lymph nodes and skin were increased. In AD+ASIT group, the inflammation of the skin was reduced, the number of infiltrated eosinophils and mast cells were decreased, and concentration of IL-4 in lymph node homogenate was reduced.Conclusion Repeated stimulation of back skin by dinitrofluorobenzene and dust mites can induce atopic dermatitis-like damage and Th2 response dominated in BABL/c mice. Desensitization treatment can improve the inflammatory skin lesions. This study is an exploration and supplement of the mouse desensitization model and provides a reference basis for the research of follow-up desensitization treatments.