加味止嗽散平喘作用及其机制实验研究
摘要
目的：研究加味止嗽散(MZ)平喘的有效部位及质控标准，在此基础上，进一步研
究MZ镇咳、化痰、抗炎和平喘作用及其平喘的作用机制。
方法：采用植化分离和药理实验相结合的活性跟踪法，筛选MZ中具有镇咳、化痰、
抗炎、平喘的有效部位，并对其进行质量控制。建立小鼠氨水引咳模型、小鼠酚红
排泄模型、二甲苯致小鼠耳肿胀模型、组胺和乙酰胆碱混合喷雾法致豚鼠支气管痉
挛哮喘模型，观察MZ的镇咳、化痰、抗炎和平喘作用；通过对卵蛋白致敏哮喘豚鼠
的肺病理学、超微结构、细胞因子的观测，对免疫器官重量的影响，对离体气管条
的作用，研究MZ平喘作用的机制。
结果：MZ被分离为极性较大部位(MZS)和极性较小部位(MZC)，有效成分集中在
MZC中。MZ、MZC具有明显的延长小鼠咳嗽潜伏期和减少咳嗽次数、增加小鼠酚红排
泄量、减轻二甲苯致小鼠耳肿胀度和延长由Ach和His引起的豚鼠跌倒潜伏期的作
用；明显抑制致敏哮喘豚鼠血液和BALF中的EOS数目和ET-1、NO、BALF中蛋白质
含量的升高；明显减轻哮喘豚鼠肺部炎症，改善超微结构的病变；显著降低小鼠肺
组织和血清中MDA含量，提高SOD活性；一定程度地增加小鼠免疫器官重量，调节
小鼠脾细胞培养上清中IL-4和IFN-γ的含量；体外明显抑制由Ach和His引起的
豚鼠支气管平滑肌的收缩作用，解除由Ach和His引起的豚鼠支气管平滑肌的痉挛。
结论：MZ具有镇咳、化痰、抗炎和平喘作用，而MZC是MZ中镇咳、化痰、抗炎和
平喘的有效部位。其作用机制可能与抑制Ach和His引起的支气管痉挛，减少体内
EOS数目，纠正Th_1／Th_2细胞和ET-1／NO之间的失衡，增加SOD活性，提高机体的抗
炎、免疫和抗氧化能力等作用有关。
Objective: To offer the gist of controlling Modified Zhi Sou San's (MZ's ) quality, and to study the anti-asthma anti-tussive expectorant anti-inflammatory effects and its mechanism.
Methods : The active parts having anti-asthma anti-tussive expectorant anti-inflammatory effects were selected by the activity extract method with phytochemistry and pharmacology. Models of anti-tussive experiments in mice with cough were induced by ammonia water and expectorant experiments were used the mice with phenol red excretion method . The inflammatory models were caused by dimethylbenzene. Bronchial spastic asthma was induced by histamine and acetylcholine in guinea pigs and the model of sensitized guinea pigs were caused by egg albumin. The anti-asthma mechanism was observed by isolated tracheas, lung tissue and other cytokine. Results: Modified Zhi Sou San was divided two parts. The low fat-soluble part was called MZS and the high fat-soluble part was called MZC. MZC could prolong their cough latent period and decrease their cough frequency, could increase secretion of phenyl red in the airway in mice, could prolong latent period of bronchial asthma in guinea pigs and relieve the mouse ear swe
lling remarkably. Under the light microscopy pathological changes in the lung tissue were obviously lighten. The content of MDA was reduced remarkably in serum and lung tissue, while the activity of SOD was elevated significantly. The number of eosinophilias and the contents of ET-1 and NO in the BALF and blood were descended remarkably. MZC could increase weights of thymus and spleen of mouse to certain degree. It could adjust the level of IL-4 and IFN- γ in supernatant of mouse spleen cells. It could reduce isolated tracheas contraction caused by acetylcholine and histamine.
Conclusion: MZ had cough relieving, expectorant, anti-inflammatory and anti-asthma effects. MZC was MZ's effective part. The mechanism by which MZC anti-asthma may be related to reducing the bronchial contraction and descending the number of EOS and adjusting the ratio of Th1/Th2 and ET-l/NO and increase the activity of SOD . MZC could enhance anti-inflammatory and antioxidant effects.
究MZ镇咳、化痰、抗炎和平喘作用及其平喘的作用机制。
方法：采用植化分离和药理实验相结合的活性跟踪法，筛选MZ中具有镇咳、化痰、
抗炎、平喘的有效部位，并对其进行质量控制。建立小鼠氨水引咳模型、小鼠酚红
排泄模型、二甲苯致小鼠耳肿胀模型、组胺和乙酰胆碱混合喷雾法致豚鼠支气管痉
挛哮喘模型，观察MZ的镇咳、化痰、抗炎和平喘作用；通过对卵蛋白致敏哮喘豚鼠
的肺病理学、超微结构、细胞因子的观测，对免疫器官重量的影响，对离体气管条
的作用，研究MZ平喘作用的机制。
结果：MZ被分离为极性较大部位(MZS)和极性较小部位(MZC)，有效成分集中在
MZC中。MZ、MZC具有明显的延长小鼠咳嗽潜伏期和减少咳嗽次数、增加小鼠酚红排
泄量、减轻二甲苯致小鼠耳肿胀度和延长由Ach和His引起的豚鼠跌倒潜伏期的作
用；明显抑制致敏哮喘豚鼠血液和BALF中的EOS数目和ET-1、NO、BALF中蛋白质
含量的升高；明显减轻哮喘豚鼠肺部炎症，改善超微结构的病变；显著降低小鼠肺
组织和血清中MDA含量，提高SOD活性；一定程度地增加小鼠免疫器官重量，调节
小鼠脾细胞培养上清中IL-4和IFN-γ的含量；体外明显抑制由Ach和His引起的
豚鼠支气管平滑肌的收缩作用，解除由Ach和His引起的豚鼠支气管平滑肌的痉挛。
结论：MZ具有镇咳、化痰、抗炎和平喘作用，而MZC是MZ中镇咳、化痰、抗炎和
平喘的有效部位。其作用机制可能与抑制Ach和His引起的支气管痉挛，减少体内
EOS数目，纠正Th_1／Th_2细胞和ET-1／NO之间的失衡，增加SOD活性，提高机体的抗
炎、免疫和抗氧化能力等作用有关。
Objective: To offer the gist of controlling Modified Zhi Sou San's (MZ's ) quality, and to study the anti-asthma anti-tussive expectorant anti-inflammatory effects and its mechanism.
Methods : The active parts having anti-asthma anti-tussive expectorant anti-inflammatory effects were selected by the activity extract method with phytochemistry and pharmacology. Models of anti-tussive experiments in mice with cough were induced by ammonia water and expectorant experiments were used the mice with phenol red excretion method . The inflammatory models were caused by dimethylbenzene. Bronchial spastic asthma was induced by histamine and acetylcholine in guinea pigs and the model of sensitized guinea pigs were caused by egg albumin. The anti-asthma mechanism was observed by isolated tracheas, lung tissue and other cytokine. Results: Modified Zhi Sou San was divided two parts. The low fat-soluble part was called MZS and the high fat-soluble part was called MZC. MZC could prolong their cough latent period and decrease their cough frequency, could increase secretion of phenyl red in the airway in mice, could prolong latent period of bronchial asthma in guinea pigs and relieve the mouse ear swe
lling remarkably. Under the light microscopy pathological changes in the lung tissue were obviously lighten. The content of MDA was reduced remarkably in serum and lung tissue, while the activity of SOD was elevated significantly. The number of eosinophilias and the contents of ET-1 and NO in the BALF and blood were descended remarkably. MZC could increase weights of thymus and spleen of mouse to certain degree. It could adjust the level of IL-4 and IFN- γ in supernatant of mouse spleen cells. It could reduce isolated tracheas contraction caused by acetylcholine and histamine.
Conclusion: MZ had cough relieving, expectorant, anti-inflammatory and anti-asthma effects. MZC was MZ's effective part. The mechanism by which MZC anti-asthma may be related to reducing the bronchial contraction and descending the number of EOS and adjusting the ratio of Th1/Th2 and ET-l/NO and increase the activity of SOD . MZC could enhance anti-inflammatory and antioxidant effects.
引文
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