母乳活性成分与儿童过敏性疾病发生的相关机制研究

The incidence rate of IgE-mediated allergic disease(AD) in children is more than 20%. Environmental agents like feeding pattern may be one of the inducing factors. This study aims to investigate the correlation between specific bioactive components in human milk and development of children's allergic disease. The study will be designed as prospective cohort study and maternal-child pairs will be as the research subjects and be followed up in this research. Bioactive factors like transforming growth factor-β (TGF-β1), Polyunsaturated Fatty Acids (PUFAs) , correlative interleukin (IL) and specific immunoglobulin E (IgE) in human milk of two groups infant with or without allergic disease will be detected, breast feeding (BF) period of both groups is >= 4 months. Family history of allergic disease and maternal dietary status at pregnancy and lactation will be collected. The relationship between specific bioactive components of human breastmilk and that of serum in mother and children will be evaluated. The concentration difference of correlation human milk high risk factors of allergic disease will be compared at two groups infant with or without allergic disease. The fast increase of these diseases can be blocked by dietary management in stead of pharmacological interference which is extremely expensive for the society.

儿童过敏性疾病（Allergic disease , AD）发病率＞20%，基因和环境因素可能是其影响因素，其中婴幼儿的喂养方式可能是诱因。本项目试图探索母乳中的生物活性因子是否与儿童过敏性疾病的发生机制相关。采用前瞻性队列研究方法，对出生队列的母子配对样本进行纵向随访，检测母乳喂养≥4个月、发生或不发生过敏性疾病的两组小儿其母乳中转化生长因子β1 (TGF-β1)、长链多不饱和脂肪酸（LCPUFAs）、相关白介素及特异性IgE的浓度；采集过敏性儿童的家族史及孕期和哺乳期母亲膳食状况；评估母乳中的特异性生物活性因子与母亲静脉血、小儿静脉血中相应生物活性因子的相关性；比较有或者无过敏性疾病的小儿其母乳乳汁过敏相关因子浓度的差异，探索母乳生物活性因子在过敏性疾病发病中的影响力度。具有潜在重大意义。

研究背景：儿童过敏性疾病（AD）增长迅速原因除基因外，还与环境和生活方式（喂养方式）改变有关。目前就母乳是AD的保护还是危险因素尚有争议，其中生物活性因子与AD关系及发生机制仍有待研究。研究内容：采用前瞻队列、母子配对样本进行纵向随访，检测有或无AD小儿其母乳中TGF-β1、LCPUFAs、白介素及IgE的浓度差异；调查AD家族史；评估母乳与母、子血中相应生物因子相关性；探索母乳生物活性因子在AD发病中的影响力度。重要结果：①母乳喂养儿AD发病现状：0-岁、1-岁小儿湿疹、6-岁鼻炎、食物过敏、哮喘患病率分别为45.2%和14.3%；33.3%、17.8%和2.4% ②早期湿疹对AD具长期影响：1-岁湿疹其6-岁AD风险更高(RR=4.857,P=0.001）③遗传的影响：有AD家族史儿童湿疹(RR=2.532,P=0.048)、过敏性鼻炎(RR=4.170,P=0.005)发病明显高于无者。④母乳∑n-3和∑n-6对AD的影响：0-岁湿疹组母乳∑n-6、LA、n-6:n-3和GLA明显高于非湿疹组。6-岁鼻炎组DHA明显低于、n-6:n-3、C20:3n-6明显高于非鼻炎组。食物过敏组母乳GLA明显高于非过敏组。⑤母亲过敏与否，其母乳脂肪酸及免疫因子差异明显且相互影响：母过敏性皮炎组母乳ALA、∑n-3较低，而n-6:n-3、LA/ALA则明显高于非皮炎组。母过敏性鼻炎组乳汁∑n-3、ALA、EPA、DHA明显低于非鼻炎组。食物过敏组母乳C20:3n-3明显高于非过敏组。无过敏的母亲乳汁ALA、EPA、∑n-3与sCD14呈正相关，C20:2n-6与sCD14呈负相关；EPA、EPA+DHA与IgE呈负相关。过敏母亲乳汁C20:3n-3与sCD14呈正相关，LA/ALA与sCD14呈负相关；C20:3n-6、GLA与IL-1β呈正相关；C22:2n-6与Eotaxin呈正相关。关键数据及其科学意义：①婴儿早期湿疹对免疫系统及应答影响深远。AD家族史、母乳高n-6、GLA和高比例n-6:n-3、低DHA是婴儿AD高危因素。②无论过敏与否，母乳中多种n-3与保护性因子sCD14呈正相关，与IgE呈负相关；多种n-6与sCD14呈负相关，与Eotaxin和强炎因子IL-1β呈正相关。表明母体LCPUFAs可能对母亲免疫因子的分泌具有一定调节作用。