射干止咳胶囊缓解感染后咳嗽及对花生四烯酸代谢通路的影响

Effects of Shegan Zhike capsule on relieving post - infectious cough and inhibiting arachi⁃donic acid metabolism pathway

目的 探讨射干止咳胶囊镇咳作用的量效、时效关系及对花生四烯酸代谢通路的影响。方法 采用浓氨水诱发小鼠咳嗽模型,观察射干止咳胶囊镇咳作用的量效、时效关系,并利用电刺激迷走神经诱发豚鼠咳嗽试验加以验证。采用烟熏建立豚鼠慢性支气管炎模型,观察射干止咳胶囊对花生四烯酸代谢通路中关键酶环氧化酶2(COX_(2))和下游代谢产物前列腺素E_(2)(PGE_(2))、血栓素A_(2)(TXA_(2))的影响。结果 射干止咳胶囊在43.00 mg提取物/kg、86.00 mg提取物/kg、172.00 mg提取物/kg剂量下能明显减少小鼠咳嗽次数(P<0.05或P<0.01);在43.00 mg提取物/kg剂量下给药5 d、7 d均有明显镇咳作用(P<0.05或P<0.01);射干止咳胶囊低剂量组(26.00 mg提取物/kg)、中剂量组(52.00m g提取物/kg)、高剂量组(104.00m g提取物/kg)有明显抑制电刺激豚鼠迷走神经所致咳嗽的作用(P<0.05或P<0.01);与模型对照组比较,射干止咳胶囊低、中、高剂量组豚鼠血清中COX_(2)、PGE_(2)、TXA_(2)含量明显降低(P<0.01)。结论 射干止咳胶囊具有明显的镇咳作用,其机制可能与抑制COX_(2)表达,减少花生四烯酸下游代谢产物PGE_(2)、TXA_(2)等炎性介质的产生有关。

Objective To explore the dose-effect and time-effect relationship of antitussive effect of Shegan Zhike capsule and its effect on arachidonic acid metabolic pathway.Methods The mouse cough model induced by concentrated ammonia was used to ob⁃serve the dose effect and time effect relationship of the antitussive effect of Shegan Zhike capsule,which was verified by the cough test of guinea pigs induced by electrical stimulation of vagus nerve.The model of chronic bronchitis in guinea pigs was established by smoking,and the effects of Shegan Zhike capsule on cyclooxygenase 2(COX_(2))and metabolites prostaglandin E_(2)(PGE_(2))and thromboxane A_(2)(TXA_(2))in arachidonic acid metabolic pathway were observed.Results Shegan Zhike capsule could significantly reduce the number of coughs in mice at the doses of 43.00 mg extract/kg,86.00 mg extract/kg and 172.00 mg extract/kg(P<0.05 or P<0.01).Shegan Zhike capsule had obvious antitussive effect at the dose of 43.00 mg extract/kg for 5 days and 7 days(P<0.05 or P<0.01).Shegan Zhike capsule low dose group(26.00 mg extract/kg),medium dose group(52.00 mg extract/kg)and high dose group(104.00 mg extract/kg)could significantly inhibit the cough caused by electrical stimulation of vagus nerve in guinea pigs(P<0.05 or P<0.01).Compared with the model control group,the contents of COX_(2),PGE_(2) and TXA_(2) in se⁃rum of guinea pigs in the low,medium and high dose groups of Shegan Zhike capsules were significantly decreased(P<0.01).Conclusion Shegan Zhike capsule had obvious antitussive effect,and its mechanism may be related to inhibiting the expression of COX_(2) and reducing the production of downstream metabolites PGE_(2) and TXA_(2) of arachidonic acid.