双氢青蒿素、甲硝唑及两药联合应用体外抗阴道毛滴虫效果的研究

The Study on the Effect of Dihydroartemisinin,Metronidazole and Mixure of the Two Drugs on Trichomonas Vaginalis in Vitro

目的观察双氢青蒿素(DHA)、甲硝唑及两药合用体外抗阴道毛滴虫的效果。方法用肝汤培养基37℃无菌培养阴道毛滴虫滋养体。每实验管含滴虫2.5×106个/ml。实验分4组:双氢青蒿素组,甲硝唑组,两药合用组,对照组。观察不同药物浓度,不同作用时间杀滴虫效果。用杀虫率评价两药合用的杀虫效果。结果两药联合应用有以下特点:(1)增效作用明显,两药配伍剂量合适时杀虫效果最佳;(2)杀虫时间缩短,双氢青蒿素1.0mg/ml+甲硝唑0.004mg/ml杀虫率为100%的时间比单用减少8h;(3)药物用量减少,同在8h,杀虫率近100%,双氢青蒿素单用最低药量为1mg/ml,甲硝唑单用最低药量为0.008mg/ml,两药合用最低药量为双氢青蒿素0.5mg/ml+甲硝唑0.004mg/ml。两药合用药量比单用各减少1倍。双氢青蒿素破坏虫膜,裂解死亡,甲硝唑主要作用于胞内结构,两药作用靶位不同是联合应用增效的基础。结论双氢青蒿素、甲硝唑杀虫机理各不相同,两药联合应用有明显增效作用。

Objective To study the effect of dihydroartemisinin（DHA）, metronidazole and mixure of the two drugs on Trichomonas vaginalis in vitro. Methods The trophozoites of T.vaginalis were cultivated in liver extract solution medium that contained 2.5×10^6 parasites/ml. DHA,metronidazole and mixure were put in the experimental tubes,respectively,which were divided into 4 groups：one normal control group,and the other three groups of DHA,metronidazole and mixure of the two drugs. Their effects of anti- T.vaginalis were observed for different periods of time of drug action in different drug concentrations. The mortality was calculated to evaluate the effect of the mixture of the two drugs. Results The effect of the mixture of the two drugs had the following features： （ 1 ）the distinct synergism：the compound of DHA and metronidazole was most effective in killing T.vaginalis. （2）the time of killing was shortened：the time for 100% mortality of T.vaginalis treated with DHA 1 mg/ml plus metronidazole 0.004 mg/ml was 16 hours,8 hours shorter than that of the single drug. （3）the drug amount was reduced：the amount needed for 100% mortality of T.vaginalis treated with DHA,metronidazole and mixture of the two drugs for 8 h was 1mg/ml,0.008 mg/ml,and 0.5 mg/m and 0.004 mg/ml;the drug amount of mixture of the two drugs decreased by 100%. The cell membrane of these parasites treated with DHA was damaged and the splitting parasites died. Metronidazole mainly acted on the interior structures. This difference in action location was synergenic base of the mixture of two drugs. Conclusion The anti-T.vaginalis mechanisms of DHA and metronidazole are dlfferent,so the mixture has obviously intensive action on T.vaginalis and may be a potential resource to obtain a more effective and less hamaful compound drug for trichomoniasis.