吸入用丙卡特罗可抑制组胺诱导的豚鼠气道过敏性炎症引起的气流阻塞和微血管渗漏。

Inhaled procaterol inhibits histamine-induced airflow obstruction and microvascular leakage in guinea-pig airways with allergic inflammation.

作者信息

Mirza Z N, Tokuyama K, Arakawa H, Kato M, Mochizuki H, Morikawa A

机构信息

Department of Paediatrics, Gunma University School of Medicine, Maebashi, Japan.

出版信息

Clin Exp Allergy. 1998 May;28(5):644-52. doi: 10.1046/j.1365-2222.1998.00263.x.

DOI:10.1046/j.1365-2222.1998.00263.x

PMID:9645602

Abstract

BACKGROUND

Beta2-adrenoceptor agonists (beta2-agonists) are shown to inhibit airway microvascular leakage in experimental animals. This effect may change in animals with chronic airway inflammation.

OBJECTIVE

We examined whether inhaled beta2-agonists inhibit microvascular leakage in guinea-pig airways with chronic allergic inflammation.

METHODS

Three weeks after the sensitization with ovalbumin (OA; 6 mg/mL), each guinea pig was challenged with inhaled OA once a day for 1 or 3 weeks. Control animals without sensitization with OA also inhaled vehicle for OA (saline) for 3 weeks. One day after the last challenge, different doses of inhaled procaterol (1, 3 or 10 microg/mL) or vehicle was given to animals for 10 min after an anaesthesia. Fifteen minutes after the end of inhalation, the animals were given i.v. Evans blue dye (EB dye; 20 mg/kg), a marker of microvascular leakage, and then i.v. histamine (3 or 30 microg/kg) or vehicle. Lung resistance, a parameter of airflow obstruction, was measured for 6 min and the lungs were removed to calculate the amount of extravasated EB dye into the airways.

RESULTS

A significant increase in eosinophil infiltration into the airways was seen in sensitized and challenged animals compared with control animals without sensitization. Among animals receiving antigenic exposure for either 0 (control), 1 or 3 weeks, 10 microg/mL procaterol significantly inhibited 30 microg/kg histamine-induced increase in EB dye extravasation to a similar degree (ranged from 28.7 to 69.8% inhibition) as well as that in lung resistance (more than 90% inhibition in all groups). The minimal dose of procaterol to inhibit 3 microg/kg histamine-induced microvascular leakage was not different between nonsensitized control animals and those sensitized and challenged for 3 weeks at all airway levels.

CONCLUSION

Inhaled beta2-adrenoceptor agonists may be also potent in attenuating microvascular leakage even in the airways with chronic allergic inflammation.

摘要

背景

β2肾上腺素能受体激动剂（β2激动剂）在实验动物中可抑制气道微血管渗漏。在患有慢性气道炎症的动物中，这种效应可能会发生变化。

目的

我们研究了吸入性β2激动剂是否能抑制慢性过敏性炎症豚鼠气道中的微血管渗漏。

方法

用卵清蛋白（OA；6mg/mL）致敏3周后，每只豚鼠每天吸入OA进行激发，持续1周或3周。未用OA致敏的对照动物也吸入OA的赋形剂（生理盐水）3周。在最后一次激发后1天，麻醉动物后给予不同剂量的吸入性丙卡特罗（1、3或10μg/mL）或赋形剂，持续10分钟。吸入结束15分钟后，给动物静脉注射伊文思蓝染料（EB染料；20mg/kg），这是微血管渗漏的标志物，然后静脉注射组胺（3或30μg/kg）或赋形剂。测量气流阻塞参数肺阻力6分钟，然后取出肺脏以计算渗漏到气道中的EB染料量。

结果

与未致敏的对照动物相比，致敏和激发的动物气道中嗜酸性粒细胞浸润显著增加。在接受抗原暴露0（对照）、1或3周的动物中，10μg/mL丙卡特罗显著抑制30μg/kg组胺诱导的EB染料外渗增加，抑制程度相似（范围为28.7%至69.8%），对肺阻力的抑制也相似（所有组均超过90%）。在所有气道水平，未致敏的对照动物与致敏并激发3周的动物相比，抑制3μg/kg组胺诱导的微血管渗漏所需的丙卡特罗最小剂量无差异。