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[微卡对哮喘豚鼠气道收缩和炎症的影响]

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

作者信息

Zhao Xiao-yan, Xie Qiang-min, Chen Ji-qiang, Bian Ru-lian

机构信息

Zhejiang Respiratory Drugs Research Laboratory of State Drugs Administration of China, Medical School of Zhejiang University, Hangzhou 310031, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2003 Apr;26(4):218-22.

Abstract

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.

摘要

目的

在豚鼠哮喘模型中研究母牛分枝杆菌(M. vaccae)对肺功能、气道高反应性和气道炎症的影响。

方法

用卵清蛋白(OVA)诱导71只豚鼠患哮喘。测定肺阻力(R(L))和动态肺顺应性(C(dyn))的变化、支气管肺泡灌洗液(BALF)中炎症细胞的积聚以及气管平滑肌对卡巴胆碱的体外收缩反应曲线。

结果

以单剂量肌肉注射(i.m)的方式用母牛分枝杆菌预处理,以剂量依赖的方式抑制了致敏豚鼠哮喘的早期阶段。2.5μg组R(L)(1分钟至15分钟)增加46.4%,7.5μg组增加29.6%,22.5μg组增加20.8%,分别显著低于模型对照组(95.3%)(P<0.05至0.01)。2.5μg组C(dyn)的平均降低率为26.8%,7.5μg组为23.5%,22.5μg组为21.5%,分别显著低于模型对照组(38.7%)(P<0.05)。以2.5μg、7.5μg和22.5μg(每只豚鼠)的剂量肌肉注射母牛分枝杆菌预处理也抑制了哮喘的晚期阶段。2.5μg组BALF中的白细胞总数为(16.2±3.2)×10⁸/L,7.5μg组为(14.6±3.4)×10⁸/L,22.5μg组为(15.4±2.5)×10⁸/L,分别显著低于模型对照组(22.3±2.2)×10⁸/L(P<0.01至0.001)。2.5μg组BAL嗜酸性粒细胞计数为(11.6±3.0)×10⁸/L,7.5μg组为(6.0±1.5)×10⁸/L,22.5μg组为(2.2±1.7)×10⁸/L,分别显著低于模型对照组(15.9±5.2)×10⁸/L(P<0.01至0.001)。母牛分枝杆菌显著抑制了致敏豚鼠气管平滑肌(TSM)中卡巴胆碱诱导的气道高反应性。2.5μg组的半数有效浓度(EC₅₀)(使TSM收缩值从基线增加50%所需的卡巴胆碱浓度)为0.140μmol/L,7.5μg组为0.179μmol/L,22.5μg组为0.236μmol/L,均高于模型对照组(0.038μmol/L)。

结论

在该动物模型中发现母牛分枝杆菌可改善肺功能、抑制气道炎症和气道高反应性,这支持其在哮喘治疗中的应用。

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