【作者】 胡燕；

【导师】 黎海芪；

【作者基本信息】 重庆医科大学 ， 儿科学， 2002， 博士

【摘要】 食物过敏是儿童营养中一个重要的社会健康问题，婴幼儿是一个特殊易感人群。虽然对食物过敏研究多年，但对其发病机制仍不清楚，尤其在国内，儿童食物过敏问题尚未引起足够重视。因此食物过敏成为影响我国儿童健康的潜在危险因素之一。本课题研究涉及（1）流行病学研究获得重庆地区婴幼儿食物过敏的患病率；（2）采用高效液相色谱分析技术对食物过敏患儿肠粘膜屏障功能进行检测；（3）通过母鼠妊娠期食物抗原暴露对仔代免疫功能影响的研究，寻求早期预防的关键期；（4）经建立口服致敏的动物模型，从组织学和免疫学等方面探讨其发病机制，从而为进一步研究食物过敏发生机制和治疗方法奠定实验基础。本研究得到如下结果和结论：1． 首次在国内开展食物过敏流行病学研究，获得0~24月儿童食物过敏的患病率（5.2%）；婴儿期是食物过敏的易感年龄。2． 治疗食物过敏唯一有效的方法是避免特定食物抗原的摄入；适当延长母乳喂养的时间对减少婴儿食物过敏的发生有帮助。收集5小时尿标本发现，尿中乳果糖及甘露醇排出率比值（L/M）显著增加（0.18±0.06 vs 0.05±0.03）（P<0.001），提示食物过敏儿童肠粘膜屏障功能发生了改变。这是国内对食物过敏患儿肠道屏障<WP=7>3． 功能进行的首次研究。4． 采用高效液相色谱仪通过双糖吸收试验检测肠道通透性的方法简便、准确性高、重复性好，是临床评价肠粘膜屏障功能的实用方法。缩短尿标本收集时间至2小时与5小时一样可检测出肠道通透性的改变。本实验方法的改良在国内外尚属首次报道，便于其推广应用。5． 母鼠妊娠期食物抗原暴露对仔鼠免疫功能的影响研究显示，妊娠晚期OVA腹腔注射可引起新生仔鼠OVA特异性淋巴细胞增殖反应增强（SI为4.40±2.86 vs 1.29±0.22）和产生IFN-γ的能力下降(66.38±31.12 vs 1293.25±1166.29pg/ml)。提示妊娠期母亲食物抗原可经胎盘途径引起胎儿淋巴细胞（尤其是T细胞）致敏，致敏窗口期为妊娠晚期。这在国内外尚属首次报道。6． 胎儿期经OVA致敏的小鼠成年后再次接触OVA，可导致OVA特异性IgE增加（0.891±0.109 vs 0.166±0.115 OD Unit），即出现OVA过敏易感性。7． 口服致敏的动物模型结果显示，采用持续单纯口服OVA的致敏方法建立动物模型是研究食物过敏发病机制的适宜模型；OVA致敏后4周OVA特异性IgE抗体明显升高(0.689±0.439 vs 0.235±0.062 OD Unit)；致敏后6周小鼠可诱导出迟发超敏反应。本研究首次在国内完全模拟人类成功建立食物过敏模型，为进一步研究食物过敏发生机制和治疗方法奠定实验基础。更多还原

【Abstract】 Food hypersensitivity(FH) is one of the most important health problems in the field of child’s nutrition because it often occurs in infants. Although FH has been studied for many years, the mechanisms of it are still unknown. So FH is one of the potential risk factors of child health. In this study, we got the prevalence of FH in 0~24months young children through epidemiology study. To determine the intestinal barrier function in the children with FH, we investigated the intestinal permeability by high performance liquid chromatography(HPLC). With two studies on animals, this paper also obtained the critical period of prophylaxis and studied the mechanisms of FH by histopathology and immunology. The results and conclusions are as follows.1. The prevalence of FH in 0~24months children is about 5.2% and the infants aged 0~12months are more susceptible to have FH.This is the first study on the epidemiology of FH in our country.<WP=10>2. The only effective treatment for FH is to avoid the offending food; The incidence of FH may be decreased by prolonging breast feeding for infants.3. A significant rise in 5-hour urinary L/M excretion ratios was found in FH children(0.18±0.06) compared to that of normal children(0.05±0.03)（P<0.001）.The intestinal barrier function was changed in children with FH.This is the first study on the intestinal barrier function of children with FH in China.4. The determination of the urinary lactulose/mannitol(L/M) excretion ratio by HPLC may be a reliable method to evaluate intestinal barrier function in clinical practice.And we are the first to report that 2-hour urine collection may be better for evaluating the intestinal permeability.5. Our study is the first to show that a higher OVA-specific lymphocyte proliferation(stimulation index is 4.40±2.86 vs 1.29±0.22)and a lower capacity to product IFN-γ(66.38±31.12 vs 1293.25±1166.29pg/ml) in the newborn mice were induced by OVA intraperitoneal injection to female mice during the late period of gestation.Therefore, transplacental priming of the fetal lymphocyte(especially T-cell) can be occurred. There was an opportunity for fetus to expose to food antigens during the intrauterine period,and the sensitization period or "window" is postulated as the late of the intrauterine life.<WP=11>6. Transplacental priming favors the development of the allergic phenotype when the mice were exposed to OVA during early life of their birth.7. BALB/c mice may be a suitable animal for studying the onset of FH to OVA upon exposure via enteral route without the use of adjuvants. The level of OVA-specific IgE (0.689±0.439 OD Unit)was increased after 4 weeks sensitization compared to that of the controls(0.235±0.062 OD Unit). The delayed type hypersensitivity responses can be elicited when the mice were sensitized for 6 weeks.This is the first animal model to mimic human FH in China.更多还原