目的:基于正交试验,研究三拗汤的配伍关系。方法:运用正交设计法,将三拗汤组方药材按L16(43)正交表配伍分为16组。BALB/c小鼠每组16只,共256只,雌雄各半。采用卵白蛋白(OVA)致敏、激发的方法复制小鼠哮喘模型,1,8d分别皮下致敏,第15～28 d 5%OVA溶液雾化激发,每次雾化前分别ig给予相应配伍配比三拗汤水煎液。第29天检测气道反应性、血液中EOS、支气管肺泡灌洗液(BALF)中EOS和白细胞总数、肺组织及气管组织病理改变。综合分析各指标优选三拗汤最优配比。验证实验中将48只BALB/c小鼠分为3组,空白组、模型组、最优配比组,每组16只,雌雄各半,以同样的方法造模并检测指标。结果:根据综合评分,三拗汤的最优配伍配比为麻黄6g,杏仁9 g,甘草3 g,其主次关系为:麻黄>杏仁>甘草。验证实验结果,其气道反应性、血液及BALF中EOS和白细胞总数、肺及气管病理改变与模型(A1B1C1)相比有显著差异(P<0.01)。结论:三拗汤该配比与临床常用配比相近,试验所得组方主次关系符合三拗汤组方原则。
Objective:San’ao Decoction(三拗汤,SAD),as a representative Chinese medicine(CM)formula, was chosen to evaluate the effect of airway inflammation and hyperresponsiveness on the lipopolysaccharide (LPS)enhanced asthma model.Methods:The asthma model was reproduced in the Balb/C mice sensitized by ovalbumin(OVA),challenged by OVA and LPS.After Balb/C mice’s administration of a dose(0.0024 g/kg)of dexamethasone acetate,and three doses(2.2 g/kg,4.4 g/kg and 8.8 g/kg)of SAD,airway inflammation and responsiveness were observed.The airway inflammation was detected by counting bronchoalveolar lavage fluid (BALF)cells and lung histopathology.Also,differential expressions of interferon-r(IFN-γ),interleukin-4(IL-4), and IL-5 in the supernatants of BALF were examined.The changes in airway responsiveness indicated by lung resistance(R_L)and stimulated by acetylcholine(Ach)were determined.Results:Small-dose SAD hardly inhibit airway inflammation or hyperresponsiveness in the LPS-enhanced asthma,while medium-dose and high-dose SAD significantly inhibited the airway hyperresponsiveness,and to some extent,reduced airway inflammation. Meanwhile,the small-dose,medium-dose,and high-dose SAD promoted Th1-type cytokines(IFN-γ)and reduced Th2-type cytokines(IL-4,IL-5)to different extents,which led to a Th1/Th2 balance.Conclusion:SAD has a good therapeutic effect on airway hyperresponsiveness in the LPS-enhanced asthma model,but its definite influence on airway inflammation is not remarkable.
