论文部分内容阅读
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 To observe the combined effect of BCG neonatal vaccination and respiratory syncytial virus (RSV) infection on experimental asthma in mice. Methods Newborn mice were divided into 5 groups: control group, OVA group, BCG + OVA group, RSV + OVA group and BCG + RSV + OVA group. All the groups except the control group were treated with asthma OVA sensitization and challenge. Alveolar hyperresponsiveness was measured within 24 h after the last challenge. Bronchoalveolar lavage was performed. The number and classification of leukocytes in bronchoalveolar lavage fluid (BALF) were observed. The levels of cytokines in bronchoalveolar lavage fluid (BALF) and serum levels of OVA Specific IgE levels, lung tissue HE staining inflammatory pathological analysis. Results (1) The total number of leucocytes and the number of all kinds of inflammatory cells in BALF in asthmatic group were significantly higher than those in control group. The total white blood cell count, eosinophil and lymphocyte count in the BCG + OVA group were significantly lower than those in the other asthma groups (P <0.05 or 0.01). (2) Compared with the control group, the level of IL-4 in BALF of asthmatic group was significantly increased (P <0.05) and the level of IFN-γ was significantly decreased (P <0.05). There was no significant difference between the 4 asthmatic groups . There was no significant difference in the levels of IL-10 between experimental groups. (3) The serum levels of OVA-specific IgE in each asthma group were significantly higher than those in the control group (P <0.05 or 0.01), and there was no significant difference between each asthma group. (4) With the increase of inhaled methacholine concentration, the airway reactivity of each group increased obviously. The airway reactivity of RSV + OVA group and BCG + RSV + OVA group was the highest, followed by OVA group, BCG + OVA group and control group. There was no significant difference between RSV + OVA group and BCG + RSV + OVA group. (5) Inflammatory score in asthma group was significantly higher than that in control group. The percentages of peribronchitis and peri-bronchial eosinophil infiltration in BCG + OVA group were significantly lower than those in the other three groups (all P <0.05), and the alveolar inflammation was significantly lower than that in OVA group and BCG + RSV + OVA group (all P < 0.05). Conclusion Neonatal BCG vaccination attenuates asthma inflammation and airway hyperresponsiveness in a mouse model of OVA sensitized / challenged asthma, but this anti-asthmatic effect may be reversed by RSV infection.