替格瑞洛在气管中的分布及对气管平滑肌的影响

The distribution of ticagrelor in trachea and its effect on tracheal smooth muscle

目的:检测小鼠气管组织中替格瑞洛的分布;考察替格瑞洛对豚鼠气管平滑肌的作用。方法:36只雄性小鼠,灌胃给予替格瑞洛24 mg·kg^(-1),采用高效液相色谱-串联质谱(HPLC-MS/MS)法测定气管组织中替格瑞洛的浓度;用Labchart电生理记录仪测定豚鼠(39只)气管螺旋条在替格瑞洛不同浓度时的张力值,以及替格瑞洛孵育前后乙酰胆碱、磷酸组胺引起气管收缩的张力值。结果:给药1 h后,替格瑞洛在支气管的分布达到最大值,为(254.74±83.22) ng·g^(-1);39例豚鼠中有5例(12.8%)在给予低浓度替格瑞洛(52.2 ng·mL^(-1))后气管螺旋条收缩,在低浓度替格瑞洛(52.2 ng·mL^(-1))孵育15 min后给予乙酰胆碱,气管平滑肌收缩张力(1.13±0.33)g比孵育前直接给予乙酰胆碱刺激的张力(1.08±0.29)g增加(P<0.05),磷酸组胺无明显此现象。结论:替格瑞洛在小鼠气管中有较大的分布浓度,可增加乙酰胆碱对豚鼠支气管平滑肌的收缩作用。

OBJECTIVE To detect the distribution of ticagrelor in mouse tracheal tissue and to investigate the effects of ticagrelor on guinea pig tracheal smooth muscle.METHODS Thirty-six male mice were given ticagrelor at 24 mg·kg^(-1) by intragastric administration.The concentrations of ticagrelor in tracheal tissues were determined by HPLC-MS/MS;Labchart electrophysiological recorder was used to record the tension values of trachea spiral strips of guinea pigs(39)at different concentrations of ticagrelor.And the tension value of tracheal contraction induced by acetylcholine and histamine phosphate before and after ticagrelor incubation.RESULTS After 1h administration,the bronchial distribution reached(254.74±83.22)ng·g^(-1),which was the maximum;it was found that 5 of 39 guinea pigs(12.8%)showed contraction of tracheal spiral strip after low concentration of ticagrelor(52.2 ng·mL^(-1)).After incubation for 15 min with low concentration of ticagrelor(52.2 ng·mL^(-1)),the systolic tension of acetylcholine stimulation was(1.13-0.33)g,which was higher than(1.08-0.29)g,which was the tension without incubation(P<0.05).Histamine phosphate did not show this effect.CONCLUSION Ticagrelor has a large distribution concentration in the trachea of mice,which can increase the contraction effect of acetylcholine on guinea pig bronchial smooth muscle.