标准化粉尘螨疫苗免疫治疗哮喘小鼠气道炎症的实验研究  

Efficacy and mechanism of standardized dermatophagoides farinae allergen sublingual vaccine in a mouse asthma model

作　　者：刘晓宇[1] 闫浩[1] 李盟[1] 李荔[1] 刘志刚[1] 喻海琼[2] 

机构地区：[1]深圳大学过敏反应与免疫学研究所,518060 [2]广州医学院呼吸病国家重点实验室,510182

出　　处：《免疫学杂志》2011年第12期1029-1032,共4页Immunological Journal

基　　金：国家863计划项目(2006AA02A231);国家自然科学基金(81071388;30760082);深圳市科技计划三新重点项目(200902);深圳大学科研创新团队基金(T200904)

摘　　要：目的建立小鼠粉尘螨过敏性哮喘模型,探讨标准化粉尘螨疫苗免疫治疗的疗效及机理。方法 32只Balb/c小鼠随机分为阴性对照组(A组)、哮喘模型组(B组)、粉尘螨疫苗低剂量治疗组(C组)、粉尘螨疫苗高剂量治疗组(D组)。A组始终给予生理盐水,B、C、D组腹腔注射50μg粉尘螨提取液和2 mg Al(OH)3免疫小鼠致敏。然后分别用PBS(50μl)、100μg、1 mg的粉尘螨粗提液皮下注射进行免疫治疗,各组用粉尘螨抗原(50μg/50μl)滴鼻激发,末次激发后24 h用气道高反应仪检测小鼠气道反应性;处死小鼠,收集支气管肺泡灌洗液(BALF)、血清以及取出小鼠的脾细胞进行后续检测。结果 B组、C组肺泡灌洗液中细胞总数和嗜酸性细胞数显著升高,气道反应性明显增强,两组相比无显著性差异。与之相比,D组气道反应性明显下降,肺泡灌洗液中细胞总数和嗜酸性细胞数显著降低(P<0.01)、Der.f特异性抗体IgE显著降低、支气管肺泡灌洗液上清中IL-4降低(P<0.05),IL-10、IFN-r的含量显著增高(P<0.05),细胞增殖反应显示D组受抑制。结论粉尘螨疫苗可以有效抑制哮喘模型肺部炎症变化和降低气道高反应性,其疗效与剂量有关,机制可能与调节Th1/Th2平衡有关。The aim of this study is to investigate the efficacy and mechanism of standard Dermatophagoides farinae（Der.f） vaccine based on the establishment of a mouse model induced by Dermatophagoides farinae.Total of 32 Balb/c mice were randomly divided into 4 groups.Group A（normal control） was treated with saline（100 μl） all the time;group B,C and D were sensitized intraperitoneally with dust mite extracts（50 μg）＋ 2 mg Al（OH）3 and then subcutaneously treated with PBS（50 μl）,100 μg Der.f,or 1 mg Der.f,followed by intranasal challenge with 50 μg Der.f.Twenty-four hours after the last challenge,the airway hyper-reactivity of mice were assayed by using whole-body plethymography,and the mice were sacrificed for collecting BALF,serum and spleen.The lung histology of mice in B and C group showed that eosinophils infiltration developed in the airways;the lung inflammation and AHR in D group were significantly alleviated than that of group B and C.Total cells and eosinophils in BALF were increased in group B and C;compared with group B and C,AHR and inflammation of group D were greatly reduced,furthermore,the numbers of total cells and eosinophils of group D were greatly decreased（P 〈 0.01）.In comparison with group B,group D showed that Der.f-specific IgE were significantly decreased,IL-4 in BALF was significantly decreased（P 〈 0.05）,but IFN-γ and IL-10（P 〈 0.05） in BALF was significantly increased.Allergen-specific proliferation of splenocyte was also inhibited in group D,but group C did not demonstrated no significant difference,as compared with group B.In sum our research suggest that Der.f subcutaneous immunotherapy can dose-dependently inhibit airway allergic inflammation and local intolerance may be involved in its mechanism.

关 键 词：粉尘螨 疫苗 哮喘 免疫治疗 机理 

分 类 号：R392.32[医药卫生—免疫学]