抗原致哮喘豚鼠气道渗出及BRL55834的作用

Antigen induced airway leakage in asthmatic guinea pigs and the effects of BRL 55834 on it

目的探讨钾通道激动剂在抗哮喘中的意义。方法１０只正常豚鼠和１７只致敏豚鼠分５组。麻醉后行右颈动、静脉和气道插管，机械通气。静脉注射阿托品和心得安各１ｍｇ／ｋｇ，３０分钟后静脉注射二甲亚砜（ＤＭＳＯ）或钾通道激动剂ＢＲＬ５５８３４，２分钟后静脉注射伊文氏蓝（ＥＢ）３０ｍｇ／ｋｇ，１分钟后雾化吸入卵蛋白（ＯＡ，３ｍｇ／ｍｌ）３０秒。结果（１）正常豚鼠气道渗出量小，ＢＲＬ５５８３４（８μｇ／ｋｇ）对正常豚鼠气道渗出无明显影响；（２）ＯＡ使致敏豚鼠气道渗出明显增加，与正常豚鼠相比，分别为气管：８７±１９（纳克染料／毫克组织）／５３±７（纳克染料／毫克组织）；主支气管：１１９±６７（纳克染料／毫克组织）／７９±４６（纳克染料／毫克组织）；肺内中央气道：６５±４４（纳克染料／毫克组织）／４６±１７（纳克染料／毫克组织）和肺内外周气道５０±３１（纳克染料／毫克组织）／３２±４（纳克染料／毫克组织），Ｐ均＜００５。（３）与对照剂ＤＭＳＯ相比，ＢＲＬ５５８３４抑制ＯＡ诱发气道渗出，增加剂量对肺内气道渗出抑制作用更强，静脉注射ＢＲＬ５５８３４８μｇ／ｋｇ时，抑制率为气管：４８％（Ｐ＜０．０５）；主支气管：５７％（Ｐ＜０．０１?

Objective To understand the role of airway leakage in asthma attack and investigate the effects of BRL 55834 on prophylaxis and treatment of asthma. Method Ten normal and seventeen sensitized guinea pigs were divided into 5 groups. After being anesthetized, right carotid artery, right jugular vein and trachea were cannulated to monitor systemic blood pressure,inject drugs, mechanical ventilate and record airway insufflation pressure (AIP). All animals were pretreated with atropine and propranolol (1 mg/kg) 30 min before experiment. DMSO or BRL 55834 was administered intravenously 2 min before intravenous injection of evans blue (EB, 30 mg/kg), Ovalbumin (OA, 3 mg/ml) was inhaled using an ultrasonic nebulier for 30 seconds 1 min after injection of EB. Result (1) BRL 55834 (8 μg/kg) did not inhibit airway leakage in normal guinea pig; (2) Airway leakage increased in sensitized guinea pigs significantly after inhaling OA, 87±19 ng dye/mg tissue vs 53±7 ng dye/mg tissue in trachea (Tr); 119±67 ng dye/mg tissue vs 79±46 ng dye/mg tissue in main bronchus (MB); 65±44 ng dye/mg tissue vs 46±17 ng dye/mg tissue in central pulmonary airway (CiPA) and 50±31 ng dye/mg tissue vs 32±4 ng dye/mg tissue in peripheral pulmonary airway (PiPA, P <0.05). (3) BRL 55834 inhibited airway leakage contrast to DMSO, especially in CiPA and PiPA, with an inhibition of 48% (Tr, P <0.05)、57%(MB, P <0.01)、44%(CiPA, P <0.05)、and 46% (PiPA, P <0.05) after injection of BRL 55834 8 μg/kg, and 46% (Tr, P <0.05)、57% (MB, P <0.01), 56%(CiPA, P <0.01) and 55% (PiPA, P <0.01) after injection of BRL 55834 16 μg/kg, respectively. (4) BRL 55834 decreased base AIP in all groups, and inhibited OA induced AIP increasing in sensitized guinea pigs, with an inhibition of 49% (BRL 55834 8 μg/kg) and 57% (BRL 55834 16 μg/kg) in contrast to DMSO. BRL 55834 had a little side effect on cardiovascular system, but without statistical significance. Conclusion Airway leakage is one of the most important components in asthma attack, BRL 55834, a selective potassium channel activator, not only decreases airway leakage, but also inhibits OA induced increase in airway resistance. All these are beneficial to prophylaxis and treatment of asthma.