目的 观察不同剂量卡介苗核酸(Bacille Calmette-guerin DNA , BCG-DNA)在不同干预时间对哮喘小鼠气道高反应性及气道炎症的干预作用。方法 1.将Balb/c雌鼠随机分为哮喘模型组、NS对照组、BCG- DNA干预组。干预组根据干预的时间和干预制剂剂量的不同分为-7DNA1 μg、-7DNA10 μg、-7DNA100 μg、10DNA1 μg、10DNA10 μg、10DNA100 μg、17DNA1 μg、17DNA10 μg、17DNA100 μg组。2.在末次激发48小时后,测定各浓度级乙酰甲胆碱激发下的增强的呼气间歇 (Enhanced Pause, Penh)值,将其与小鼠激发前吸入NS后的Penh的百分比(Penh%NS),作为其气道反应性评价指标;其次对肺泡灌洗液进行细胞学分析。结果 1.气道反应性:①-7DNA1 μg组从Mch为3.12～50 mg/mL之间的Penh%NS显著低于哮喘组(P<0.05);②-7DNA10 μg组和-7DNA 100 μg组从Mch为6.25～25 mg/mL之间的Penh%NS显著低于哮喘组(P<0.05);③10DNA10 μg组从Mch为12.5～25 mg/mL之间的Penh%NS显著低于哮喘组(P<0.05);④10DNA100 μg组从Mch为3.12、12.5～50 mg/mL之间的Penh%NS显著低于哮喘组(P<0.05);⑤17DNA1 μg组在Mch为3.12、12.5 mg/mL的Penh%NS显著低于哮喘组(P<0.05);⑥17DNA10 μg组在Mch为12.5 mg/mL之间的Penh%NS显著低于哮喘组(P<0.05) 2.气道炎症:10DNA1 μg、-7DNA10 μg、10DNA10 μg和17DNA10 μg组的BALF细胞分类Eos%分别为:35.34±3.81、27.30±6.91、38.20±6.56、42.17±5.17;显著低于哮喘组的Eos%(48.8±6.12)(P<0.05);10DNA1 μg组的Eos%显著低于-7DNA1 μg组的Eos%(P<0.05);-7DNA10 μg组的Eos%显著低于10DNA10 μg、17DNA10 μg、-7DNA1 μg和-7DNA100 μg组的Eos%(P<0.05)。结论 BCG-DNA能降低哮喘小鼠的气道高反应性,减轻哮喘小鼠的气道炎症,早期(－7 d)中小剂量的干预效果较佳。

Objective To investigate the effect of Bacille Calmette-Guerin BCG-DNA on airway hyperresponsiveness and airway inflammation in asthmatic mouse model. Methods 1.According to different intervention, mouse were divided into asthma groups, NS control group, BCG-DNA group. According to different time and dosage intervened with asthma model, the BCG-DNA group were subdivided into -7DNA1 μg、-7DNA10 μg、-7DNA100 μg、10DNA1 μg、10DNA10 μg、10DNA100 μg、17DNA1 μg、17DNA10 μg and 17DNA100 μg group. 2.48 hours after the final incitation, the mice were stimulated with increasing concentrations of methacholine, and the airway resistance was measured. Enhance pause (Penh) was taken for each group. Bronchoalveolar lavage cytology was performed to evaluate the airway inflammation. Results 1.Airway hyperresponsiveness: ① Penh%NS of-7DNA1 μg group was significantly lower than the asthma group when Mch was 3.12~50 mg/mL (P<0.05); ② Penh%NS of -7DNA10 μg group and -7DNA100 μg group were significantly lower than the asthma group when Mch was 6.25~50 mg/mL (P<0.05);③ Penh%NS of 10DNA10 μg group was significantly lower than the asthma group when Mch was 12.5~25 mg/mL (P<0.05); ④ Penh%NS of 10DNA100 μg group was significantly lower than the asthma group when Mch was 3.12,12.5~50 mg/mL (P<0.05); ⑤ Penh%NS of 17DNA1 μg group was significantly lower than the asthma group when Mch was 3.12 or 12.5 mg/mL (P<0.05);⑥Penh%NS of 17DNA10 μg group was significantly lower than the asthma group when Mch was 12.5 mg/mL(P<0.05). 2.Airway inflammation: The Eos% of 10DNA1 μg, -7DNA10 μg,10DNA10 μg and 17DNA10 μg group (35.34±3.81、27.30±6.91、38.20±6.56、42.17±5.17) were lower than the asthma group (P<0.05); The Eos% of 10DNA1 μg group was lower than the -7DNA1 μg group (P<0.05); The Eos% of -7DNA10 μg group was lower than the 10DNA10μg, 17DNA10 μg,-7DNA1 μg and -7DNA100 μg group (P<0.05). Conclusion BCG-DNA can inhibit the airway inflammation and hyperresponsiveness in asthmatic mouse model. Early interventions with middle dose bring better results.