吸入糖皮质激素对哮喘豚鼠肺内SP含量及基因表达的影响研究(英文)

Effect of glucocorticoid on substance P content and mRNA expression in lungs of guinea pigs with asthma

摘要:

目的 P物质 (SP)是气道非胆碱能兴奋性神经的重要递质 ,是导致哮喘气道神经源性炎症产生的一种重要感觉神经肽。糖皮质激素是否有降低肺内SP的效应尚不清楚 ,为此本文研究了吸入糖皮质激素对哮喘豚鼠肺内SP的影响及其分子机制。方法 30只豚鼠用卵蛋白致敏、诱喘制成哮喘动物模型 ,随机分为哮喘组和治疗组 (每组 1 5只 ) ,另 1 5只豚鼠吸入生理盐水作为对照组。治疗组豚鼠在诱喘前 1天、诱喘当天及诱喘后 2 4h吸入丙酸倍氯米松雾化溶液。哮喘组和治疗组豚鼠均于诱喘后 2 4h取材 ,对照组同期取材 ,分别留取支气管肺泡灌洗液 (BALF)、血浆及肺组织标本。用放射免疫放法检测SP蛋白含量 ;用反转录多聚酶链式反应检测肺组织SPmRNA相对含量。结果 哮喘组豚鼠血浆、BALF及肺组织SP含量 [(1 2 2± 4 6 )pg/mL ,(90± 39) pg/mL ,(78±15 )pg/克蛋白 ]均明显高于正常对照组 [(84± 33) pg/ml,(32± 2 1 ) pg/ml,(4 2± 1 2 ) pg/ml]及激素治疗组 [(5 0±1 3) pg/mL ,(4 7± 2 0 )pg/mL ,(4 0± 1 3) pg/克蛋白 ],其差异均有显著性 (P <0 .0 1 ) ;激素治疗组血浆SP含量低于正常对照组 (P <0 .0 5 ) ,BALF及肺组织SP含量与对照组比较 ,差异无显著性 (P >0 .0 5 )。哮喘组豚鼠肺组织中SPmRNA相对含量明显高于正常

Abstract:

Objective Substance P (SP) is an important transmitter of non cholinergic excitatory nerves in the lung and can cause neurogenic inflammation in the airway of asthma. It is not know whether inhalation of glucocorticoids (GCs) can decrease the SP contents in lungs. This paper aims at studying the effect and molecule mechanism of GCs on the SP level. Methods Thirty guinea pigs were used to establish asthma models and were randomly assigned into a GCs treated asthma group and an Asthma group without treatment (n=15 each). The GCs treated asthma group received the beclomethasone dipropionate (BDP) aerosolized solution on the day before asthma inducement, on the day of inducement and 24 hrs after inducement. The SP contents in the plasma, brorchoalveolar lavage fluid (BALF) and lung tissues were detected by radioimmunoassay and the SP mRNA expression in the lung tissues was assayed by RT PCR technique 24 hrs after asthma inducement. Fifteen normal guinea pigs, which inhaled normal saline, were used as the Normal control group. Results The SP contents in the plasma, BALF and lung tissues (122±46 pg/ml, 90±39 pg/ml, 78±15 pg/g) in the Asthma group without treatment were significantly higher than those of the Normal control group (84±33 pg/ml, 32±21) pg/ml, and 42±12 pg/g respectively) and the GCs treated asthma group (50±13 pg/ml, 47±20 pg/ml and 40±13 pg/g respectively) (all P< 0.01 ). The plasma SP content in the GCs treated asthma group was lower than that of the Normal control group (P< 0.05 ), while the BALF and lung tissue SP contents did not differ from the Normal control group. The SP mRNA expression in the lung tissues in the Asthma group without treatment ( 1.0 ± 0.02 ) was significantly higher than that of the Normal Control group ( 0.2 ± 0.05 ) and the GCs treated asthma group ( 0.3 ± 0.06 )( both P< 0.01 ), and no significant difference was found between the GCs treated asthma group and the Normal control group. Conclusions Glucocorticoid can significantly down regulate SP mRNA expression and decrease the SP contents in plsma, BALF and lung tissues in asthmatic guinea pigs.