湖北贝母总生物碱平喘作用及其机理的研究

Studies on the Antiasthmatic Effect and Mechanisms of the Total Alkaloids from Fritillaria hupehensis in Guinea Pigs

目的研究湖北贝母总生物碱对豚鼠的平喘作用及其机理。方法采用豚鼠整体动物引喘和豚鼠离体气管螺旋条的实验方法,分别研究湖北贝母总生物碱对乙酰胆碱-组胺(Ach-Histamine)整体动物的平喘作用、对离体气管平滑肌基础张力的影响及对各种致痉剂收缩气管平滑肌的抑制作用。结果湖北贝母总生物碱在4 mg/kg剂量下灌胃给药1 h后,能明显延长Ach-Histamine所致豚鼠哮喘的引喘潜伏期,表现出良好的平喘效应;对豚鼠离体气管平滑肌的基础张力无显著影响;对Histamine和5-HT引起的收缩也无明显的抑制作用;但对于Ach引起的收缩,湖北贝母总生物碱在2.5mg/L的浓度时即呈现出显著的抑制作用(P<0.01),对20μmol/L Ach的IC50为13.130 4 mg/L;湖北贝母总生物碱可使Ach量效累积曲线向右平移,而最大效应不降低。结论湖北贝母总生物碱对豚鼠具有较强的平喘作用,其机理可能与竞争性拮抗气管平滑肌M受体从而扩张气管平滑肌作用有关。

Objective To investigate the antiasthmatic effect and its mechanism of the total alkaloids from Fritillaria hupehensis in guinea pigs. Methods We investigated the antiasthmatic effect of the total alkaloids through observing the latent period of asthma induced by acetylcholine - histamine in guinea pigs. By measuring the tension of isolated guinea pig tracheal strips in vitro, we observed the influence of the total alkaloids from Fritillaria hupehensis both on the basal tension and the contraction induced by acetycholine, histamine and 5 - HT. Results 4 mg/ kg （ i. g） of the total alkaloids could significantly prolong the latent period of asthma in guinea pigs. In the isolated guinea pig tracheal smooth muscle experiments, though the total alkaloids from Fritillaria hupehensis could not change the basal tension and the contraction induced by histamine and 5 - HT, it could antagonize the contraction induced by acetylcholine. The IC50 was 13. 130 4 mg/L. Moreover, the cumulative concentration - response curves of acetylcholine were shifted to the right in a concentration - dependent manner, and the maximal contraction was not changed significantly. Conclusion The total alkaloids from Fritillaria hupehensis has obvious autiasthmatic effect, which may be correlated with the competitive antagonism of musearinic receptor on guinea pig tracheal smooth muscle. The total alkaloids from Fritillaria hupehensis may be an novel and good antiasthmatic agent.