丁苯酞对豚鼠平喘作用的初步药效学观察

目的：初步探讨丁苯酞对豚鼠的平喘作用及机制。方法：本次研究分为离体气管平滑肌实验与动物整体实验两部分。在离体实验中制备豚鼠离体气管片，使用Ach、Hist使气管平滑肌收缩达到最大值后，按累积加药法加入丁苯酞，记录1、10、100 mg/L丁苯酞对痉挛气管平滑肌的解痉作用（n=10）。在整体实验中，取经筛选的豚鼠分为正常对照组、模型对照组、地塞米松组及丁苯酞高、低剂量组（n=8），在吸入低浓度激发液（1% ACh：0.05% Hist=1：1）激发6次（每次10 s）的基础上，第7次吸入高浓度激发液（2% ACh：0.1% Hist=1：1）10 s，观测90 mg/kg、30mg/kg丁苯酞对哮喘豚鼠行为学以及血清NO、支气管肺泡灌洗液（BALF）中ET-1的影响。结果：1、10、100 mg/L的丁苯酞对ACh、Hist引起的离体痉挛状态的豚鼠气管平滑肌有显著的解痉作用（对Ach的解痉率为15.08 ±7.68、42.41 ±13.54、77.56 ±24.82；对Hist的解痉率为19.40 ±7.60、56.84 ±11.72、76.35 ±19.40）且呈一定的量效关系（P< 0.05，0.01）；在乙酰胆碱与组胺的引喘下，90 mg/kg、30 mg/kg丁苯酞能明显延长豚鼠的哮喘潜伏期（53.3 ±13.2、33.1 ±13.0），改善哮喘行为学，降低血清NO（78.71 ±19.40、84.75 ±20.97）、支气管肺泡灌洗液（BALF）中ET-1（24.30 ±5.80、28.50 ±6.31）的含量（P < 0.05，0.01）。结论：丁苯酞具有一定的平喘作用，而缓解NO、ET-1异常升高是其作用机制之一。

Preliminary pharmacodynamics study on antiasthmatic action of butylphthalide in guinea pig

Objective: To study the anti-asthmatic effects of butylphthalide in guinea pig. Methods: This research included isolated tra-cheal smooth muscle and in vivo animal experiments. Antispasmodic effects of butylphthalide at the concentrations of 1, 10, 100 mg/L were observed through spasmodical tracheal smooth muscle of guinea pig induced by acetylcholine or histamine (n=10). After screened, the guinea pigs were divided into control group, model group, dexamethasone(DXM) group, high and low dose butylphthalide groups. The effects of butylphthalide on nitric oxide (NO), endothelin-1 (ET-1) and asthmatic behaviors were observed on the asthmatic guinea pigs that were stimu-lated six times by the excitation fluid (1% ACh:0.05% Hist=1:1). Results: Butylphthalide at the concentrations of 1、10、100 mg/L had an-ti-spasmodic effects on spasmodical tracheal smooth muscle of guinea pig (15.08 ±7.68、42.41 ±13.54、77.56 ±24.82 to acetylcholine, 19.40 ±7.60、56.84 ±11.72、76.35 ±19.40 to histamine), which showed a certain dose-effect relationship. Butylphthalide could prolong asth-matic incubation period (53.3 ±13.2、33.1 ±13.0), improve asthmatic behaviors, reduce NO in serum (78.71 ±19.40、84.75 ±20.97) and ET-1 in bronchoalveolar lavage fluid (24.30 ±5.80、28.50 ±6.31) (P < 0.05, 0.01). Conclusion: Butylphthalide has some effects of anti-asthma and one of the mechanisms is to relieve abnormal increase of NO and ET-1.