吸入糖皮质激素对哮喘患儿血浆及支气管诱导痰液中P物质含量的影响及其机制研究

Effect of inhaled corticosteroid (Budesonide)on substance P in plasma and induced sputum in children with bronchial asthma and its mechanism

目的研究吸入糖皮质激素(GC)对哮喘患儿血浆及支气管诱导痰液(BIS)中P物质(SP)含量变化的影响并对其机制进行探讨。方法选择临床确诊的轻、中度哮喘患儿50例,随机分成吸入GC(布地奈德雾化溶液)治疗组(组1)及非吸入GC治疗组(组2)各25例,健康对照组20例。用放射免疫(RI)方法,测定各组治疗前及治疗后48h血浆及BIS中SP含量变化。用吸入卵蛋白致敏法制作豚鼠哮喘模型30例,随机分成吸入GC组及非吸入GC组,用RI法检测各组血浆、支气管肺泡灌洗液(BALF)及肺组织中SP含量;用RT_PCR法检测肺组织中SPmRNA相对含量。结果入院后48h比较,组1血浆及BIS中SP含量较治疗前降低明显,差异有非常显著性(P<0.01),组2较治疗前降低,但差异无显著性(P>0.05);治疗后48h同期比较,组1血浆及BIS中SP含量较组2明显降低,差异有非常显著性(P<0.001);哮喘组豚鼠血浆、BALF、肺组织中SP含量及SPmRNA表达均明显高于正常组豚鼠,差异有显著性(P<0.01);吸入GC组哮喘豚鼠,其血浆、BALF、肺组织中SP含量及SPmRNA表达均明显低于非吸入GC组哮喘豚鼠,差异有显著性(P<0.05或0.01)。结论吸入GC具有明显降低哮喘患儿血浆及支气管诱导痰液中SP含量的作用,并可显著降低哮喘豚鼠血浆、BALF及肺组织中SP含量,其机制可能与吸入GC具有在转录水平下调肺组织中SPmRNA表达有关。

Objectives To investigate the effect of inhaled corticosteroid （Budesonide） on substance P （SP） in plasma and induced sputum in children with bronchial asthma and to explore its mechanisms. Methods （1） Clinical research. Fifty asthmatic children were enrolled in this study. All subjects suffered from mild to moderate asthma and had no history of corticosteroid administration 3 days prior to admission. Patients were randomly divided into group A （inhaling Budesonide） and group B （no inhalation）.Twenty health children at the same age were as control. The contents of SP in plasma and induced sputum were detected by radioimmunoassay for each group before and 48 hours after treatment. （2）Animal studies：Thirty guinea pigs were sensitized and challenged with exposure to aerosolized ovalbumin for establishing animal asthma model. These animals were randomly divided into inhaled Budesonide group and no inhalation group. Normal control group （n = 15） were treated with NS inhalation instead of ovalbumin and Budesonide. The contents of SP in the plasma, bronchoalveolar lavage fluid （BALF） and lung tissues were detected by radioimmunoassay, and the expression of SPmRNA in lung tissues was examined by RT- PCR. Results （1） The contents of SP in the plasma and induced sputum in children with bronchial asthma in group A were significantly lower 48 hours after treatment than those in before （P〈 0.01）, but no significant difference in group B （P〉0.05）. （2） The contents of SP in the plasma and induced sputum in group A were significantly lower than those in group B 48 hours after treatment （P〈0.01）. （3） The contents of SP in the plasma, BALF, lung tissue and SPmRNA expression of asthma group were significantly higher than normal control group （P〈0.01）. （4） The contents of SP in the plasma, BALF, lung tissue and SP mRNA expression of inhaled Budesonide group were significantly lower than those of no inhalation group （P〈0.01） . Conclusions Inhaled corticosteroid （Budesonide） can significantly decrease the contents of SP in plasma and induced sputum in children with bronchial asthma and can significantly decrease the contents of SP in plasma, BALF and lung tissues of guinea pigs with induced asthma. The mechanism of the effect may be related to the down-regulation of SPmRNA expression in lung tissues caused by corticosteroid （Budesonide）.