气态甲醛诱发过敏性哮喘分子机理的系列研究

Molecular mechanism of allergic asthma induced by gaseous formaldehyde

目的①以甲醛作为模型化合物,探索非过敏原性空气污染物与过敏症和哮喘的因果联系;②寻找联系二者的分子机理。方法①甲醛所致获得性过敏体质小鼠模型的制备;②甲醛诱导型过敏性哮喘的大鼠模型的制备;两种动物模型的成功建立,为进一步研究预防和治疗这类过敏症和哮喘病提供了可靠的实验基础;③甲醛诱发小鼠发生过敏体质和/或哮喘的分子机理的研究,其中包括:A.甲醛通过第二类类香草受体信号传递系统对Th2淋巴细胞系统的激活作用;B.甲醛通过胸腺基质淋巴细胞生成素(TSLP)对Th2淋巴细胞系统的激活作用;C.甲醛通过上调GSNOR(S-nitrosog lutathione reductase,GSNOR)表达,解除GSNO对气道畅通的保护作用。结果甲醛作为非过敏原性空气污染物的模型化合物,具有诱导过敏体质生成和诱发哮喘的作用;甲醛诱发哮喘的主要途径之一是活化Th2淋巴细胞系统,导致机体形成获得性过敏体质;解除GSNO对气道畅通的保护作用也可能是另外一种甲醛诱发哮喘的分子机理。结论过敏症和哮喘病患者的数量在快速增长,但过敏原的种类和数量并没有发生明显的变化。非过敏原性空气污染物的大量增加被认为是原因之一,但是一直没有得到令人信服的分子机理的解释。

Objective The purpose of this project：is to explore the possible relation between non-allergenlc air pollutants and asthma/allergy, and furthermore,try to clarify its molecular mechanism. Methods The study includes： ①Construction of the ＂formaldehyde-induced atopy mouse model＂ ; ② Construction of the ＂formaldehyde-induced allergic asthma rat model＂ ; The two successfully constructed animal models have provided reliable experimental basis for the research on such kind allergy and/or asthma ③ ＂ molecular mechanism of the formaldehydeinduced mice allergy and/or asthma ＂ includes ： A. Formaldehyde activation of Th2 lymphocytes via the pathway of type Ⅱ VR signaling system. B. Formaldehyde activation of Th2 lymphocytes via the pathway of thymic stromallymphocytes （TSLP） ; C. Arrestment of formaldehyde on the protective effect for expediting airway via the pathway of upregnlating the expression of GSNOR. Results The results showed ： as a model compound of ＂non-allergenic air pollutants＂, formaldehyde can induce the form of acquired atopy and asthma; One of the major pathways of formaldehyde-induced asthma is that formaldehyde can activate the Th2 lymphocytes system by way of the form of ＂acquired atopy＂. Conclusion The number of patients with allergy and asthma in the world has been growing rapidly, however, the type and level of allergens in the world have no significant change. The increase in the number of non-allergenic air pollutants was considered to be one of the reasons, yet the molecular mechanism has not been convincingly explained.