1-甲基海因对哮喘大鼠模型的平喘作用及其机制

目的：探讨1-甲基海因（1-MH）对哮喘及咳嗽动物模型的干预作用，初步阐明其作用机制。方法：选取50只Wistar大鼠，采用卵清蛋白诱发大鼠哮喘后随机分为模型对照组1-MH 20、40、80 mg?kg-1剂量组和阳性对照组（氨茶碱60 mg?kg-1），另取10只Wistar大鼠作为空白对照组。收集各组大鼠支气管肺泡灌洗液（BALF），测定白细胞介素5（IL-5）、嗜酸粒细胞趋化因子（Eotaxin）水平及嗜酸性粒细胞（EOS）计数；选取40只引喘合格豚鼠随机分为模型对照组，1-MH 15、30和60 mg?kg-1剂量组及阳性对照组（氨茶碱50 mg/kg），记录各组豚鼠哮喘发生潜伏期；选取豚鼠10只，取支气管放于Krebs液中，记录并计算0.25、0.50 和 1.00 g/L1-MH 对抗磷酸组胺的解痉百分率；选取引咳合格小鼠50只，随机分成1-MH 25、50和100 mg?kg-1剂量组及阳性对照组（可待因50 mg/kg），记录各组小鼠咳嗽潜伏期及3 min内的咳嗽次数；选取引咳合格豚鼠40只，随机分成1-MH 15、30和60 mg/kg剂量组及阳性对照组（可待因20 mg/kg），记录各组豚鼠咳嗽潜伏期及5 min内的咳嗽次数。结果：与致敏模型对照组比较，1-MH 40和80 mg/kg剂量组大鼠BALF中IL-5、Eotaxin水平及EOS计数明显降低（P<0.05或P<0.01）；与乙酰胆碱诱导哮喘模型对照组比较，1-MH 30和60 mg/kg剂量组豚鼠哮喘发生潜伏期明显延长（P<0.05或P<0.01）；与空白对照组比较，1-MH 0.50和 1.00 g/L剂量组豚鼠离体气管平滑肌的解痉百分率明显升高（P<0.01）；与小鼠咳嗽模型对照组比较，1-MH 50和100 mg/kg剂量组小鼠咳嗽潜伏期延长，咳嗽次数减少（P<0.05或P<0.01）；与豚鼠咳嗽模型对照组比较，1-MH 30和 60 mg/kg剂量组豚鼠咳嗽潜伏期延长，咳嗽次数减少（P<0.05或P<0.01）。结论：1-MH具有良好的平喘及镇咳作用，平喘作用可能与其抑制气道炎症和直接舒张支气管平滑肌有关。

Antiasthmatic effect of 1-methylhydantoin on rat asthma model and its mechanism

Objective To investigate the effect of 1-methylhydantoin(1-MH)on asthma and cough animal model, and to clarify its mechanism preliminarily.Methods 50Wistar rats with ovalbumin-induced asthma were randomly divided into model group,1-MH 20,40,and 80 mg·kg-1 groups,positive control group(aminophylline, 60mg·kg-1),another 10 Wistar rats served as control group.The levels of interleukin-5(IL-5),eosinophil chemotactic factor(Eotaxin)and eosinophil(EOS)count in bronchoalveolar lavage fluid(BALF)were measured in various groups.40 guinea pigs of asthma were randomly divided into model group,1-MH 15,30,and 60mg·kg-1 groups,positive control group(aminophylline,50 mg·kg-1);the asthma incubation period of guinea pig was measured in various groups.The bronchus of 10guinea pigs were selected and put in Krebs solution,and the antispasmodic percentages against histamine phosphate of 1-MH 0.25,0.50,and 1.00g·L-1 were recorded and calculated.50 mice of cough were randomly divided into model group,1-MH 25,50,and 100mg·kg-1 groups,positive control group(codeine,50 mg·kg-1);the cough incubation period and the number of cough in the mice were measured in various groups.40guinea pigs of cough were randomly divided into model group,1-MH 15,30,and 60 mg·kg-1 groups,positive control group(codeine,20 mg·kg-1);the cough incubation period and the number of cough of the guinea pigs in various groups were measured. Results Compared with sensitized model control group,the levels of IL-5,Eotaxin and EOS count in BALF of the rats in 1-MH 40mg·kg-1 and 80mg·kg-1 groups were reduced(P <0.05or P <0.01);compared with acetylcholine-induced asthma model control group,the asthma incubation period of guinea pig in 1-MH 30mg·kg-1 and 60mg·kg-1 groups was prolonged(P<0.05or P<0.01);compared with blank control group, the antispasmodic percentages against histamine phosphate in 1-MH 0.50g ·L-1 and 1.00g ·L-1 groups were increased(P<0.01);compared with mouse cough model control group,the cough incubation period of the mice was prolonged,the cough number of the mice was decreased in 50mg·kg-1 and 100mg·kg-1 groups(P<0.05or P<0.01);compared with guinea pig cough model control group,the cough incubation period of the guinea pig was prolonged,the cough number of the guinea pig was decreased in 1-MH 30mg·kg-1 and 60mg·kg-1 groups(P< 0.05or P<0.01).Conclusion 1-MH has good antiasthmatic and antitussive effects,which may be related to inhibition of airway inflammation and relaxation of bronchial smooth muscle directly.