摘要
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、80mg·kg-1剂量组和阳性对照组(氨茶碱60mg·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60mg·kg-1剂量组及阳性对照组(氨茶碱50mg·kg-1),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1.00g·L-11-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100mg·kg-1剂量组及阳性对照组(可待因50mg·kg-1),记录各组小鼠咳嗽潜伏期及3min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60mg·kg-1剂量组及阳性对照组(可待因20mg·kg-1),记录各组豚鼠咳嗽潜伏期及5min内的咳嗽次数。结果:与致敏模型对照组比较,1-MH 40和80mg·kg-1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60mg·kg-1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1.00g·L-1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100mg·kg-1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60mg·kg-1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。
Objective To investigate the effect of 1-methylhydantoin （1-MH）on asthma and cough animal model, and to clarify its mechanism preliminarily.Methods 50 Wistar 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, 60 mg·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＆amp;nbsp;various groups. 40 guinea pigs of asthma were randomly divided into model group, 1-MH 15, 30, and 60 mg·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 10 guinea pigs were selected and put in Krebs solution,and the antispasmodic percentages against histamine phosphate of 1-MH 0.25,0.50,and 1.00 g ·L-1 were recorded and calculated. 50 mice of cough were randomly divided into model group,1-MH 25,50,and 100 mg·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.40 guinea 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 40 mg·kg-1 and 80 mg·kg-1 groups were reduced （P〈0.05 or P〈0.01 ）;compared with acetylcholine-induced asthma model control group, the asthma incubation period of guinea pig in 1-MH 30 mg·kg-1 and 60 mg·kg-1 groups was prolonged（P〈0.05 or P〈0.01）;compared with blank control group, the antispasmodic percentages against histamine phosphate in 1-MH 0.50 g · L-1 and 1.00 g · 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 50 mg·kg-1 and 100 mg·kg-1 groups（P〈0.05 or 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 30 mg·kg-1 and 60 mg·kg-1 groups （P〈0.05 or 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 .
出处
《吉林大学学报（医学版）》
CAS
CSCD
北大核心
2014年第3期543-548,共6页
Journal of Jilin University：Medicine Edition
基金
科技部国家科技重大专项"重大新药创制"项目资助课题(2011ZX09102-011-05)
