1-甲基海因对哮喘大鼠模型的平喘作用及其机制

发布时间：2018-07-27 11:03

【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(P0.05或P0.01);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(P0.05或P0.01);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(P0.01);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(P0.05或P0.01);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(P0.05或P0.01)。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。
[Abstract]:Aim: to investigate the effect of 1-methylhydantoin (1-MH) on asthma and cough animal models and to clarify its mechanism. Methods: fifty Wistar rats were randomly divided into two groups: model control group (1-MH 2040mg kg-1) and positive control group (aminophylline 60mg kg-1) after asthma induced by ovalbumin (ovalbumin). Another 10 Wistar rats were used as blank control group. The levels of interleukin 5 (IL-5), eosinophil chemokine (Eotaxin) and eosinophil (EOS) were measured by (BALF), in bronchoalveolar lavage fluid. Forty asthmatic guinea pigs were randomly divided into the model control group (1-MH1530) and 60mg kg-1 group and the positive control group (aminophylline 50mg kg-1) to record the latent period of asthma in each group, 10 guinea pigs were selected and the bronchus was taken and put into Krebs solution. The antispasmodic percentages of 0.25g L-11-MH and 1.00g L-11-MH against histamine phosphate were recorded and calculated, 50 mice were randomly divided into two groups: 1-MH 2550 and 100mg kg-1 dosage group and positive control group (codeine 50mg kg-1). The latent period of cough and the number of cough times in 3min were recorded in each group. Forty guinea pigs were randomly divided into 1-MH 1530 and 60mg kg-1 groups and positive control group (codeine 20mg kg-1). The latent period of cough and the times of cough within 5min were recorded in each group. Results: compared with the sensitized model control group, the IL-5 eotaxin level and EOS count in the BALF of rats in the 1-MH40 and 80mg kg-1 groups were significantly decreased (P0.05 or P0.01), and the latent period of asthma in the 1-MH30 and 60mg kg-1 groups was significantly lower than that in the acetylcholine-induced asthmatic model control group (P0.05 or P0.01). Compared with the blank control group, the spasmodic percentage of isolated tracheal smooth muscle of guinea pigs was significantly increased in 1-MH 0.50 and 1.00 g L-1 groups (P0.01), and the cough latency was prolonged in 1-MH50 and 100mg kg-1 groups compared with the mouse cough model control group (P0.01). The number of cough decreased (P0.05 or P0.01), compared with the guinea pig cough model control group, 1-MH 30 and 60mg kg-1 dose group cough latency prolonged, cough times decreased (P0.05 or P0.01). Conclusion 1-MH has good antiasthmatic and antitussive effects, which may be related to its inhibition of airway inflammation and direct relaxation of bronchial smooth muscle.
【作者单位】：长春中医药大学药学院临床药学与中药药理教研室;长春中医药大学药学院药剂与炮制教研室;
【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)
【分类号】：R562.25

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