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999感冒灵主要药效学及其作用机制研究(1)
http://www.100md.com 2016年4月15日 《中国中药杂志》2016年第8期
     [摘要]观察999感冒灵全方中中药组分与化学药组分配伍后在药效学作用上的协同作用,并研究其作用机制。分别在冰醋酸致小鼠腹腔毛细血管通透性增加、二甲苯致小鼠耳肿胀和角叉菜胶致大鼠胸膜炎非特异性炎症模型和酵母菌致大鼠发热模型和肺炎克雷白杆菌细菌生物被膜(Klebsiellar pneumonia,KPN)模型上,比较感冒灵全方、化学药组分和中药组分的抗炎、解热作用的异同。结果显示,与模型组比较,感冒灵全方组小鼠伊文思蓝渗出量明显减少,小鼠的耳肿胀度明显减小,化学药组分和中药组分组均未见显著性差异;感冒灵全方组、化学药组分组、中药组分组大鼠胸腔渗出液TNFα和IL1β浓度明显降低,感冒灵全方组大鼠血清TNFα,IL1β和IL8,化学药组分组大鼠血清TNFα,IL8和中药组分大鼠血清IL8浓度明显降低;感冒灵全方组和化学药组分组大鼠分别于药后4~8 h体温升高值明显减小,中药组分组大鼠的体温升高值无明显差异。感冒灵全方在55~1375 g·L-1、中药组分在45~225 g·L-1、西药组分在10 g·L-1时可显著降低细菌生物被膜的活菌量。扫描电镜显示,感冒灵全方(55 g·L-1)和西药组分(10 g·L-1)可破坏KPN生物被膜,中药组分(45 g·L-1)可在一定程度上破坏KPN生物被膜。结果表明,感冒灵全方具有明显的抗炎和解热作用,对成熟KPN生物被膜具有破坏作用。感冒灵化学药组分和中药组分在抗炎和抑制成熟KPN生物被膜内活菌量方面显示明显的协同作用,但在解热方面未观察到明显的协同作用。

    [关键词]999感冒灵;炎症;炎性因子;肺克雷白杆菌(KPN);细菌生物被膜

    [Abstract]To observe synergistic effects of 999 Ganmaoling (GML) and its Chinese/Western materia medica (CMM and WMM) on pharmacodynamic action and to study underlying mechanisms, their antiinflammatory, antipyretic effects were compared by assaying the increased capillary permeability induced by glacial acetic acid in mice, ear swelling induced by Xylene in mice, nonspecific pleurisy induced by carrageenan in rats, and yeast induced fever in rats Crystal violet (CV) and microbial activity (XTT) assay were used to evaluate the inhibition of GML and its CMM and WMM on KPN biofilm formation, and scanning electron microscopy (SEM) was applied for observing KPN biofilm morphology changes The results showed that compared with control group, GML could reduce exudation amount of EvansBlue and the degree of Ear swelling significantly, and CMM and WMM have no significant effects The concentration of TNFα and IL1β of rat pleural effusion in GML, CMM and WMM group decreased significantly The concentration of TNFα, IL1β and IL8 in GML group, TNFα, IL8 in WMM group and IL8 in CMM in rats serum decreased significantly The body temperature in rats decreased significantly in GML and WMM group after 48 h of administration CMM group showed no significant difference in rat body temperature compare with control Compared with control group, GML (551375 g·L-1) could inhibit KPN biofilm formation and reduce number of viable cells in the KPN biofilm CMM (45225 g·L-1) and WMM (10 g·L-1) could also inhibit KPN biofilm formation and reduce number of viable cells (P<001) Result of SEM also showed that GML (55 g·L-1) and its CMM (45 g·L-1) and WMM (10 g·L-1) could interfere the bacterial arrangement of KPN biofilm and extracellular matrix GML and its CMM &WMM could inhibit the formation of KPN biofilm, CMM &WMM in GML showed synergism and complementation in inhibit KPN biofilm Results showed that GML had obvious antiinflammatory and antipyretic effects and could destruct KPN mature biofilm WMM and CMM showed obvious synergistic effect against inflammation and inhibition of KPN biofilm formation and reduction of number of viable cells but no same effects against fever (徐启华 贺蓉 彭博 叶祖光 李建荣 张跃飞 代志)
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