盐酸小檗碱与氟康唑协同抗耐药白念珠菌的动物实验

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。

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

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)(P>0.05).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)(P<0.05).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(P<0.05) and increase in dosaged berberine hydrochloride led to the same results(P<0.05 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.