对虾原肌球蛋白不同致敏途径对BALB/c小鼠致敏性的影响

Allergenicity of Shrimp Tropomyosin from Different Sensitization Approaches on BALB/c Mice

随着食物过敏现象的日益普遍,其已成为工业化国家一个严重的公众健康问题。食物蛋白致敏机理的相关研究大多借助于两大类小鼠模型,即口服致敏模型和局部或皮肤致敏模型。然而,不同模型之间的差异以及如何选择合适的模型进行研究却鲜有人关注。鉴于此,本研究旨在通过比较对虾原肌球蛋白口服灌胃和腹腔注射两种给药途径对BALB/c小鼠致敏性的影响,寻求最佳给药方式,以便建立有效的动物模型,并在分子及免疫水平研究其致敏机理,从而为食物过敏原动物模型的构建提供一定的理论依据,也为研究食物过敏原致敏机制以及预防治疗食物过敏提供重要的模型依据。结果表明,腹腔注射小鼠血清中特异性免疫球蛋白(immunoglobulin,Ig)E、组胺以及辅助性T细胞(helper T cells,Th)2型细胞因子含量均高于口服灌胃小鼠,其致敏性更好。此外,口服灌胃小鼠血清特异性Ig G2a、干扰素-γ、调节性T细胞水平增加,表明虽有黏膜佐剂作用,但口服给药仍可能使小鼠产生口服免疫耐受,从而降低对虾原肌球蛋白对其的致敏性。本研究表明,腹腔注射原肌球蛋白比口服灌胃更易使小鼠致敏,其Th1/Th2平衡被打破,Th2反应占据优势,更适合用于构建食物致敏动物模型。

Food allergy is an important public health issue in industrial countries due to the increasing prevalence and the potential life-threatening consequence. The understanding of food allergy mechanisms usually comes from experimental mouse models, which are broadly divided into two categories： oral sensitization model and topical or epicutaneous sensitization model. However, few studies have been focused on the difference between the two categories and the selection of the appropriate one. In this study, we aimed to develop a suitable route for tropomyosin administration by comparing the allergenicity of oral gavage and intraperitoneal injection in BALB/c mice in order to establish an effective animal model and to investigate the underlying mechanisms at the molecular and immunological levels, which will provide a theoretical basis for the establishment of animal model for food allergen research, the exploration of the mechanism of food allergen sensitization, and the prevention and treatment of food allergy. Results indicated that higher tropomyosin-specific immunoglobulin（Ig） E, histamine, and helper T cell（Th） type 2 cytokines were observed in intraperitoneally sensitized mice than those intragastrically sensitized, indicating that intraperitoneal injection was more sensitive in inducing systemic food allergy. Furthermore, higher levels of serum tropomyosin-specific Ig G2 a and interferon gamma, as well as regulatory T cell population were observed in intragastrically sensitized mice, suggesting that oral gavage may still develop oral tolerance to decrease the allergenicity of shrimp tropomyosin in BALB/c mice in spite of the presence of mucosal adjuvant. This experiment showed that intraperitoneal injection of tropomyosin to sensitized mice is easier than oral gavage, breaking the Th1/Th2 balance and making Th2 response dominant. Accordingly, intraperitoneal injection is more suitable to establish an animal model for food allergy research.