大鼠发育早期接触变应原对Th1/Th2亚群功能及哮喘发生的影响

目的探讨妊娠期母鼠及其子代接触尘螨点刺液（Derp）对发育后期个体Th1/Th2平衡及哮喘发生的影响。方法Wistar大鼠根据母体妊娠期及新生早期是否接触Derp随机分为对照组、母Derp-仔Derp-组（母鼠和其子代均未接触Derp）、母Derp＋仔Derp＋组（母鼠和其子代均接触Derp）和母Derp＋仔Derp-组（母鼠接触Derp,其子代未接触Derp）,分别皮下注射Derp或生理盐水,30d龄时除对照组外,其余3组以卵白蛋白（OVA）为变应原致敏并雾化吸入,诱发哮喘发生。取血浆检测OVA特异性IgE抗体、收集外周血单个核细胞（PBMC）用ELISA法检测培养上清中细胞因子IL-4和IFN-γ水平,行支气管肺泡灌洗记录支气管肺泡灌洗液（BALF）中嗜酸性粒细胞的计数,留取肺组织行病理学检查。结果母Derp＋仔Derp＋组在哮喘建模后PBMC培养上清中IFN-γ水平显著低于母Derp-仔Derp-组,IL-4水平显著升高,IL-4/IFN-γ比值升高,OVA特异性IgE、BALF中嗜酸性粒细胞计数显著高于母Derp-仔Derp-组;母Derp＋仔Derp-组与母Derp-仔Derp-组IL-4和IFN-γ水平差异均无统计学意义,OVA特异性IgE水平虽有增高,但差异不具统计学意义,BALF中嗜酸性粒细胞计数差异无统计学意义。母Derp＋仔Derp＋组Th2优势显著高于母Derp＋仔Derp-组。结论胎鼠对于Derp跨胎盘的致敏作用可通过母体妊娠期间的免疫来完成,这一过程会根本上导致Th2优势免疫的发生,增加了变态反应性疾病的危险性。

The effect of HDM allergen exposure on the Th1/Th2 balance and the development of asthma in early life of rat

Objective The prevalence rates of asthma and other atopic disorders have increased steadily over the past few decades. The underlying mechanisms for this phenomenon remain largely unknown. Since the natural mutation rate is low, altered environmental and life style conditions are thought to play an important role. High exposure to house dust mite allergens has been shown to predispose to allergic sensitization and to the development and persistence of asthma. The prenatal period and early childhood are considered to be critical for the establishment and maintenance of a normal Th1/Th2 balance. Immune modulation at this stage may be a way forward in the prevention of allergy.The aim of the study is to investigate the effect of maternal house dust mite allergen exposure during pregnancy and infant exposure in the early life on the development of asthma in an animal model. The aim is to address the best period of allergen avoidance in the prevention of allergic disease.Methods Wistar rats were divided into 4 groups according to the different treatment, control、M Der p-N Der p^-、M Der p^＋ N Der p^＋ and M Der p^＋N Der p^-（M=mater, N=neonate, ＂-＂ the rats were treated with NS instead of Der p）. A presensitization of 5 000SBU Der p was done at the 11th, 18th day of pregnancy and/or the 2nd,9th,16th day of the infant rats. All rats except control group were sensitized by intraperitoneal and subcutaneous injections of ovalbumin （OVA） and AI（OH）3 twice, then received 6 consecutive airway allergen challenges by aerosolization to develop asthma animal model when they were 30-day old. The plasma samples were obtained to determine the OVA-specific IgE antibody titers. The peripheral blood mononuclear cells （PBMC） were cultured to measure the cytokine production. Bronchoalveolar lavage and differential cell counts of BAL fluid were performed. At last, the lung tissue was prepared for analysing the pathological changes of asthma. Results In the groups which mater and infant were both exposed to Der