盐酸小檗碱与氟康唑协同抗耐药白念珠菌的动物实验

The synergistic effects of berberine hydrochloride and fluconazol on drug-resistant Candida albicans:An experimental study

目的观察盐酸小檗碱不同剂量与氟康唑协同抗耐药白念珠菌的疗效。方法将90只ICR小鼠随机分为6组,每组15只,分别为真菌感染模型组(简称:空白对照组)、单用盐酸小檗碱(9 mg/kg)治疗组(简称小檗碱组)、氟康唑(0.5 mg/kg)单用治疗组(简称氟康唑组)、盐酸小檗碱(1 mg/kg)+氟康唑(0.5 mg/kg)治疗组(简称合用1组)、盐酸小檗碱(3 mg/kg)+氟康唑(0.5 mg/kg)治疗组(简称合用2组)、盐酸小檗碱(9 mg/kg)+氟康唑(0.5 mg/kg)治疗组(简称合用3组)。在小鼠系统性真菌感染模型建立2 h后各治疗组分别腹腔注射给药0.2 ml/10 g,1次/d,连续给药7 d,肾脏的活菌数检测换算为log10CFU/值。结果单纯小檗碱组平均存活时间3.5 d,肾脏的活菌数为log10CFU/值6.566,与空白对照组3.4 d、活菌数6.462无显著性差异(P>0.05);氟康唑组平均存活时间9.9 d、活菌数为6.566,与小檗碱组有显著性差异(P<0.05);合用1组平均存活时间12.7 d、活菌数为5.723;合用2组平均存活时间16.1 d、活菌数5.645;合用3组平均存活时间18.7 d、活菌数为4.967。两药合用组的存活时间明显延长及活菌数明显低于各单用治疗组(P<0.05或0.01),其中,合用2组和3组与氟康唑单纯治疗组相比有非常显著性差异(P<0.01)。结论盐酸小檗碱与氟康唑合用有协同抗耐药白念珠菌作用,中剂量以上小檗碱合用氟康唑能显著提高耐药白念珠菌的疗效。

objective To observe the synergistic effects of berberine hydrochloride and fluconazol on drug-resistant Candida albicans.Methods Ninety ICR mouse were randomly divided into 6 groups（15 in each group）.Two hours after the systemic infection model was made,drugs were intraperitoneally given at 0.2 ml/10 g qd for 7 days.The viable bacteria in kidney biopsy sample was calculated as log10CFU/g.Results The mean survival time was no statistically significant between mouses（3.5days,with berberine hydrochloride 9 mg/kg,viable bacteria 6.566） and mouses（3.4days,with no drugs,viable bacteria 6.462）（P0.05）.The mean survival time was statistically significant between mouses（9.9days,with fluconazol 0.5mg/kg,viable bacteria 6.566） and mouses（with berberine hydrochloride 9 mg/kg）（P0.05）.The mean survival time was 12.7days in mouse administered with berberine hydrochloride（1 mg/kg）and fluconazol（0.5 mg/kg）（viable bacteria 5.723）,16.1 days in mouses with berberine hydrochloride（3 mg/kg）and fluconazol（0.5 mg/kg）（viable bacteria 5.645）,18.7days in mouses with berberine hydrochloride（9 mg/kg）and fluconazol（0.5 mg/kg）（viable bacteria 4.967）.The combined therapy resulted in longer survival than single drug therapy（P0.05） and increase in dosaged berberine hydrochloride led to the same results（P0.05 or 0.01）.Conclusion Berberine hydrochloride combined with fluconazol has synergistic effects on drug-resistant Candida albicans with moderate dosage of berberine hydrochloride combined with fluconazol leading to enhanced effect.