母牛分支杆菌菌苗对哮喘豚鼠气道收缩和炎症反应的影响

目的　观察母牛分支杆菌菌苗 (微卡 )对致敏豚鼠抗原攻击后肺功能、气道炎症 ,离体气管平滑肌高反应性的影响。方法　 71只豚鼠采用卵蛋白致敏形成豚鼠哮喘模型 ,测定肺阻力 (RL)和动态肺顺应性 (Cdyn)、支气管肺泡灌洗液 (BALF)中的炎症细胞以及卡巴胆碱 (carbachol)诱导的离体气管平滑肌高反应性。结果　微卡单次肌肉注射预处理呈量效关系抑制致敏豚鼠抗原攻击后引起哮喘速发相反应。微卡 2 .5 μg组RL(1～ 15min)平均增值为 4 6 4 % ,7 5 μg组为 2 9 6 % ,2 2 5 μg组为2 0 8% ,而模型组为 95 3% ,用药各组与模型组比较 ,差异有显著性 (P <0 0 5、<0 0 1) ;微卡 2 5 μg组Cdyn(1～ 15min)平均下降值为 2 6 8% ,7 5 μg组为 2 3 5 % ,2 2 5 μg组为 2 1 5 % ,而模型组为 38 7% ,微卡用药各组与模型组比较 ,差异有显著性 (P <0 0 5 )。微卡单次肌肉注射也能抑制哮喘的迟发相 ,微卡 2 5 μg组BALF中的白细胞总数为 (16 2± 3 2 )× 10 8/L ,微卡 7 5 μg组为 (14 6± 3 4 )× 10 8/L ,微卡2 2 5 μg组为 (15 4± 2 5 )× 10 8/L ,而模型组为 (2 2 3± 2 2 )× 10 8/L ,微卡用药各组与模型组比较 ,差异有显著性 (P <0 0 1、<0 0 0 1) ;微卡 2 5 μg组BALF中的嗜酸性粒细胞数为 (11

Effects of vaccae on airway contraction and inflammation in asthmatic guinea pigs

OBJECTIVE: To study the effects of Mycobacterium vaccae (M. vaccae) on the lung function, airway hyperresponsiveness and airway inflammation in a guinea pig model of asthma. METHODS: Asthma was induced with ovalbumin (OVA) in 71 guinea pigs. The changes of lung resistance (R(L)) and dynamic lung compliance (C(dyn)), the accumulation of inflammatory cells in bronchoalveolar lavage fluids (BALF), and the contraction reaction curve of tracheal smooth muscles to carbachol in vitro were determined. RESULTS: Pretreatment with M. vaccae as a single dosage by intramuscular injection (i.m) inhibited the early phase of asthma in the sensitized guinea pigs in a dose-dependent manner. R(L) (1 min to 15 min) increased 46.4% in the 2.5 micro g group, 29.6% in the 7.5 micro g group, and 20.8% in the 22.5 micro g group, which were significantly lower than that in the model control group (95.3%) (P < 0.05 approximately 0.01), respectively. The mean decrease of C(dyn) was 26.8% in the 2.5 micro g group, 23.5% in the 7.5 micro g group, and 21.5% in the 22.5 micro g group, which were significantly lower than that in the model control group (38.7%) (P < 0.05), respectively. Pretreatment with M. vaccae in a dosage of 2.5 micro g, 7.5 micro g and 22.5 micro g (per guinea pig) i.m also inhibited the late phase of asthma. The total white blood cells in BALF was (16.2 +/- 3.2) x 10(8)/L in the 2.5 micro g group, (14.6 +/- 3.4) x 10(8)/L in the 7.5 micro g group, and (15.4 +/- 2.5) x 10(8)/L in the 22.5 micro g group, which were significantly lower than that in the model control group (22.3 +/- 2.2) x 10(8)/L (P < 0.01 approximately 0.001), respectively. BAL eosinophil count was (11.6 +/- 3.0) x 10(8)/L in the 2.5 micro g group, (6.0 +/- 1.5) x 10(8)/L in the 7.5 micro g group, and (2.2 +/- 1.7) x 10(8)/L in the 22.5 micro g group, which were significantly lower than that in the model control group (15.9 +/- 5.2) x 10(8)/L (P < 0.01 approximately 0.001), respectively. M. vaccae significantly inhibited carbachol-induced airway hyperresponsiveness in the tracheal smooth muscle (TSM) from the sensitized guinea pigs. EC(50) (the concentration of carbachol required to increase TSM contraction value by 50% from the baseline) was 0.140 micro mol/L in the 2.5 micro g group, 0.179 micro mol/L in the 7.5 micro g group and 0.236 micro mol/L in the 22.5 micro g group, which were higher than that in the model control group (0.038 micro mol/L). CONCLUSIONS: M. vaccae was found to improve lung function, inhibit airway inflammation and airway hyperresponsiveness in this animal model, which supports its application in the treatment of asthma.