等辐射分析法研究3种白头翁皂苷抗血吸虫的相互作用

Study on the interactions of three kinds of Pulsatilla chinensis saponins against Schistosoma japonicum with isobolographic analysis

目的：采用等辐射分析法研究3种抗血吸虫的白头翁皂苷相互作用关系。方法：将血吸虫随机分成B3组（A组）、B7组（B组）、B9组（C组）、B3/B7组（D组）、B3/B9组（E组）、B7/B9组（F组）、B3/B7/B9组（G组）7组。各组给予不同剂量的单体及配伍复合药物,以血吸虫虫体活力降低率为指标,采用SPSS 11.5软件计算药物的ED50（半数有效量）,等辐射图分析3药之间的相互作用。结果：A组的ED50为21.13μg·ml-1（95%可信限为14.96～30.96μg·ml-1）,B组为2.56μg·ml-1（95%可信限1.89～3.12μg·ml-1）,C组为15.00μg·ml-1（95%可信限10.68～21.77μg·ml-1）,D组为11.02/1.92μg·ml-1（95%可信限8.05/1.31～14.41/2.47μg·ml-1）,E组为12.99/8.57μg·ml-1（95%可信限9.43/6.10～18.02/12.22μg·ml-1）,F组为1.84/2.42μg·ml-1（95%可信限1.33/1.40～2.21/3.85μg·ml-1）,G组为3.56/2.39/2.52μg·ml-1（95%可信限1.17/1.91/1.00～6.57/2.89/5.25μg·ml-1）。在研究对血吸虫的杀灭作用时,F,G组ED50偏离相加线有显著性差异（P〈0.05）,D,E组在给药前后无显著性差异（P〉0.05）。结论：等辐射分析法能方便、准确地反映出药物间的相互作用,等辐射图可知,B3/B7（剂量比6∶1）,B3/B9（剂量比3∶2）合用对血吸虫杀灭作用具有相加效应,而B7/B9（剂量比1∶1.5）,B3/B7/B9（剂量比2∶1∶1.5）具有协同效应,优化后的混合物的抗血吸虫活性优于普通提取物。

OBJECTIVE To study the interactions of three kinds of Pulsatilla chinensis saponins against Schistosoma japonicum with isobolographic analysis.METHODS The adults of Schistosoma japonicum were randomly divided into following groups：B3 group（A group）,B7 group（B group）,B9 group（C group）,B3/B7group（D group）,B3/B9group（E group）,B7/B9group（F group）,B3/B7/B9group（G group）.With the rate of reduced vitality as the index,different doses of the monomer and composite drug were given for every group to calculate the ED50（Median effective dose）by the software of SPASS11.5,and the interaction between the three kinds of drugs were analyzed by the graph of isobolographic analysis.RESULTSThe ED50 of group A was 21.13μg·ml-1（The 95%of confidence limits was 14.96-30.96μg·ml-1）,The ED50 of group B was 2.56μg·ml-1（The 95%of confidence limits was 1.89-3.12μg·ml-1）,The ED50 of group C was 15.00μg·ml-1（The95%of confidence limits was 10.68-21.77μg·ml-1）,The ED50 of group D was 11.02/1.92μg·ml-1（The 95% of confidence limits was 8.05/1.31-14.41/2.47μg·ml-1）,The ED50 of group E was 12.99/8.57μg·ml-1（The 95%of confidence limits was 9.43/6.10-18.02/12.22μg·ml-1）,The ED50 of group F was 1.84/2.42μg·ml-1（The 95%of confidence limits was 1.33/1.40-2.21/3.85μg·ml-1）,The ED50 of group G was 3.56/2.39/2.52μg·ml-1（The 95% of confidence limits was 1.17/1.91/1.00-6.57/2.89/5.25μg·ml-1）.At the end of the effect of the against Schistosoma japonicum,the ED50 of group F and G had significant difference（P〈0.05）,deviating the sum of line,but the group D and E not（P〉0.05）.CONCLUSION Isobologram is a suitable and convenient way to reveal the interaction between the three kinds of drugs for against Schistosoma japonicum.In this study,we find that the Pulsatilla chinensis saponin B3/B7（6∶1）and the B3/B9（3∶2）have a additive effect,while the B7/B9（1∶1.5）and B3/B7/B9（2∶1∶1.5）have a synergistic effect,the mixture after optimizing is superior to ordinary extract against Schistosoma japonicum.