摘要
目的:研究幼年大鼠不同时间接触卵蛋白(ovalbumin,OVA)对成年后气道哮喘炎症的影响及机制。方法:新生SD(Sprague Dawley)大鼠随机分为哮喘组,出生后第3天、第7天、第14天变应原接触组,以及正常对照组。各变应原接触组分别于出生后第3天、第7天和第14天给予皮下注射OVA1 mg(含氢氧化铝凝胶5 mg)。大鼠饲养至6周龄后,除正常对照组外其他各组均经OVA致敏并激发为哮喘模型。观察大鼠肺组织病理改变,计数每个细支气管上皮中黏液细胞数量。检测脾及胸腺中CD4+CD25+T细胞比例和叉头框P3(forkhead box P3,Foxp3)转录因子mRNA表达水平。结果:出生后第3天组(2.29±0.49)、出生后第7天组(1.25±0.46)与哮喘组相比(3.50±0.76)黏液细胞数量减少(P<0.01),气道炎症明显减轻;而出生后第14天组黏液细胞数未见减少[(3.00±1.16)vs(3.50±0.76),P>0.05]。出生后第3天组、第7天组脾中CD4+CD25+T细胞比例[(13.68±3.54)%vs(7.33±3.39)%,P<0.01;(16.65±4.91)%vs(7.33±3.39)%,P<0.01]和Foxp3 mRNA水平[(18.46±5.01)vs(5.49±1.99),P<0.01;(26.37±4.68)vs(5.49±1.99),P<0.01]与正常组比较均明显升高,且出生后第7天组胸腺中Foxp3 mRNA表达亦增高[(18.73±3.66)vs(11.13±1.75),P<0.01];但出生后第14天组脾CD4+CD25+T细胞比例及Foxp3 mRNA表达与正常组比较差异均无统计学意义[(11.04±2.88)%vs(7.33±3.39)%,P>0.05;(8.71±2.19)vs(5.49±1.99),P>0.05]。结论:早期接触变应原对大鼠哮喘气道炎症的抑制作用存在"时间窗"现象,其发生机制可能与诱导产生调节性T细胞有关。
Objective : To investigate the effect of exposure to allergen ( ovalbumin, OVA) at different times in infancy on the asthmatic airway inflammation of adult rats, and its possible mechanisms. Methods: Newborn rats were classified as asthma model group, day 3, day 7, day 14 after birth allergen exposure groups and control group, and were injected with OVA 1 mg (containing aluminum hydroxide gel 5 mg) subcutaneously on days 3, 7 and 14 after birth respectively. When all rats were kept till six weeks old, all groups but the control group were immunized and provoked via OVA to make asthma model. The pathologic changes of lung tissue and the hyperplasia of mucous cells per bronchiole were observed. The percentage of CD4^+ CD25^+T cells and forkhead box P3 (Foxp3) transcription factor mRNA in the splenocytes and thymocytes were also measured. Results: The airway inflammation alleviated significantly and number of mucous cells per bronchiole decreased significantly in day 3 group [ (2. 29 ± 0.49) vs(3.50 ± 0.76),P〈0.01] and day7 group[(1.25 ±0.46) vs( 3.50 ± 0.76), P〈0.01] compared with asthma group. However, the hyperplasia of mucous cells did not alleviate significantly in day 14 group [ (3.00 ± 1.16) vs( 3.50 ±0. 76), P 〉0. 05]. The CD4^+CD25^+T cells and Foxp3 mR- NA in the splenocytes increased in day 3 group [ ( 13.68 ± 3.54 ) % vs (7.33 ± 3.39 ) %, P 〈 0. 01 ; (18.46±5.01) vs (5.49 ±1.99), P〈0.01] and day7 group [(16.65 ±4.91)% vs (7.33 ± 3.39 ) %, P 〈 0. 01 ; (26. 37 ± 4.68 ) vs ( 5.49 ± 1.99 ), P 〈 0.01 ] compared with control group, so did Foxp3 mRNA in thymus in day 7 group [ ( 18.73 ± 3.66) vs ( 11.13 ± 1.75 ), P 〈 0.01 ]. But neither the CD4^+ CD25 ^+ T cells [ ( 11.04 ± 2. 88 ) % vs (7.33 ±3.39 ) %, P 〉 0. 05 ] nor Foxp3 mRNA expression[ (8.71±2. 19) vs( 5.49 ± 1.99), P 〉 0. 05 ] had a statistically significant increase in day 14 group. Conclusion: There exists a "time-window" for inhibiting airway inflammation by early exposure to allergen in the rat asthma model. The possible mechanism could be associated with induced generation of regulatory T cells.
出处
《北京大学学报(医学版)》
CAS
CSCD
北大核心
2008年第3期306-309,共4页
Journal of Peking University:Health Sciences
基金
国家自然科学基金资助项目(30740048)~~
关键词
哮喘
免疫耐受
T淋巴细胞
卵蛋白类
大鼠
Asthma
Immune tolerance
Regulatory T cells
Egg proteins
Rats