卡介苗新生期接种和呼吸道合胞病毒感染对小鼠实验性哮喘的联合作用  

Combined effects of neonatal Bacillus Calmette-Guerin vaccination and respiratory syncytial infection on experimental asthma in mice

作　　者：李睿[1] 刘恩梅[1] 杨锡强[2] 王莉佳[2] 

机构地区：[1]重庆医科大学附属儿童医院呼吸科 [2]重庆医科大学附属儿童医院临床免疫室,400014

出　　处：《中华儿科杂志》2006年第6期420-424,共5页Chinese Journal of Pediatrics

基　　金：国家自然科学基金资助项目(30300321)

摘　　要：目的观察卡介苗(BCG)新生期接种和呼吸道合胞病毒(RSV)感染对小鼠实验性哮喘的联合作用。方法新生期小鼠分5组:对照组、鸡卵白蛋白(OVA)组、BCG+OVA组、RSV+OVA组、BCG+RSV+OVA组,除对照组外,其他各组为哮喘组都进行OVA致敏和激发。最后一次激发后24 h内测气道高反应性,进行支气管肺泡灌洗,观察支气管肺泡灌洗液(BALF)中白细胞数及分类,ELISA方法检测肺泡灌洗液中细胞因子含量和血清中OVA特异性IgE水平,肺组织HE染色进行炎症病理学分析。结果(1)各哮喘组BALF中白细胞总数及各类炎症细胞数都比对照组显著升高。BCG+OVA组的白细胞总数、嗜酸性粒细胞和淋巴细胞计数显著低于其他哮喘组(P<0.05或0.01)。(2)各哮喘组与对照组比较BALF中IL-4水平显著增高(P<0.05),IFN-γ水平显著减低(P<0.05),4组哮喘组之间两两比较差异无统计学意义。各实验组IL-10水平差异无统计学意义。(3)各哮喘组血清中OVA特异性IgE水平都比对照组明显增高(P<0.05或0.01),各哮喘组之间比较差异无统计学意义。(4)随吸入乙酰甲胆碱浓度增加各组气道反应性明显增加。RSV+OVA组和BCG+RSV+OVA组的气道反应性最高,其后依次是OVA组、BCG+OVA组、对照组。RSV+OVA组和BCG+RSV+OVA组间比较差异无统计学意义。(5)各哮喘组的炎症评分都显著高于对照组。BCG+OVA组的细支气管周围炎症和支气管周围嗜酸性粒细胞浸润百分率显著低于另外三组(P均<0.05),肺泡炎症反应明显低于OVA组和BCG+RSV+OVA组(P均<0.05)。结论新生期BCG接种在OVA致敏/激发的小鼠哮喘模型中能减轻哮喘炎症和气道高反应性,但这种抗哮喘作用可被RSV感染逆转。Objective Neonatal Bacillus Calmette-Guerin （BCG） vaccination could decrease asthma prevalence in human according to ＂hygiene hypothesis＂. The authors proposed a hypothesis that effect of BCG vaccination on inhibiting asthma in human might be reversed by respiratory virus infection. The objective of this study was to observe combined effects of neonatal BCG vaccination and respiratory syncytial virus （RSV） infection on experimental asthma in mice. Methods Neonatal BALB/c mice were divided into five groups. Control and ovalbumin （OVA） groups were mock-vaccinated at birth and mock-infected at 3 weeks of age. BCG ＋ OVA group was BCG-vaccinated and mock-infected. RSV ＋ OVA group was mock- vaccinated and RSV-infected. BCG ＋ RSV ＋ OVA group was BCG-vaccinated and RSV-infected. Except for control group, all the other groups underwent ovalbumin （OVA） sensitization and challenge. Airway responsiveness to inhaled methacholine was measured and bronchoalveolar lavage （BAL） was performed after the last challege. Cells in BAL fluid （BALF） were counted. Cytokines in BALF and serum OVA-specific IgE were detected by ELISA and inflammatory characteristics of lungs was scored by staining with hematoxylin and eosin. Results （1） The numbers of total white cells, lymphecytes, monecytes,neutrophils, and eosinophils in the BALF from all OVA-sensitized/challenged groups were significantly greater than those in control （P 〈0. 01 ）, and BCG ＋ OVA group had significantly lower total white cells, lymphocytes and eosinophils as compared with other OVA-sensitized/challenged groups（P 〈0. 05 or 0. 01 ）. （2） All OVA-sensitized/challenged groups had significantly lower IFNT （P 〈 0. 05） and higher IL-4 （ P 〈 0.05） level in BALF as compared with control, but there was no significant difference among all OVA sensitized/challenged groups. There was no significant difference in IL-10 level between all experimental groups. （3） All OVA-sensitized/challenged groups showed significan

关 键 词：卡介苗 呼吸道合胞病毒 哮喘 小鼠 

分 类 号：R562.25[医药卫生—呼吸系统]