Misawa M, Chiba Y
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Res Commun Chem Pathol Pharmacol. 1994 Jun;84(3):341-9.
The effects of ozagrel, a thromboxane A2 (TXA2) synthase inhibitor, and CV-3988, a platelet activating factor (PAF) antagonist, was investigated on the repeatedly antigenic challenge-induced airway hyperresponsiveness (AHR) in rats. Rats were actively sensitized with DNP-Ascaris antigen and received 3 inhalations of antigen (challenges) or saline (sensitized control) every 48 hr. These animals were also pretreated with ozagrel (100 mg/kg, p.o., 30 min before), CV-3988 (3 mg/kg, i.v., 5 min before) or respective vehicle (water and saline, respectively) before each inhalation of antigen or saline. The in vivo airway responsiveness to cumulatively inhaled acetylcholine (ACh; 0.001-0.03%, each for 3 min) was measured 24 hr after the last inhalation of antigen or saline under anesthesia. A marked AHR was observed after repeated antigenic challenge when compared with the sensitized control group (5.5-9.5 times in order). This AHR was significantly, but partly, attenuated by pretreatment with ozagrel although this treatment alone had no effect on the airway responsiveness to inhaled ACh in sensitized control animals. On the other hand, CV-3988 had no inhibitory effect on this AHR. These findings suggest that TXA2, but not PAF, is one of the most important mediators participating in the pathogenesis of the antigen-induced AHR in rats.
研究了血栓素A2（TXA2）合酶抑制剂奥扎格雷和血小板活化因子（PAF）拮抗剂CV - 3988对大鼠反复抗原激发诱导的气道高反应性（AHR）的影响。大鼠用二硝基苯 - 蛔虫抗原主动致敏，每48小时接受3次抗原吸入（激发）或生理盐水吸入（致敏对照）。在每次吸入抗原或生理盐水之前，这些动物还分别先用奥扎格雷（100mg/kg，口服，提前30分钟）、CV - 3988（3mg/kg，静脉注射，提前5分钟）或各自的赋形剂（分别为水和生理盐水）进行预处理。在末次吸入抗原或生理盐水24小时后，在麻醉状态下测量对累积吸入乙酰胆碱（ACh；0.001 - 0.03%，每次3分钟）的体内气道反应性。与致敏对照组相比，反复抗原激发后观察到明显的AHR（依次为5.5 - 9.5倍）。尽管单独使用该处理对致敏对照动物吸入ACh的气道反应性无影响，但奥扎格雷预处理可显著但部分减轻这种AHR。另一方面，CV - 3988对这种AHR没有抑制作用。这些发现表明，TXA2而非PAF是参与大鼠抗原诱导的AHR发病机制的最重要介质之一。
