摘要
目的观察6种药物单独或联合用药对体外培养泡球蚴的作用。方法泡球蚴体外培养5周后,收集囊泡,随机分为17组,每组约120~140个囊泡,分别加入不同药物进行培养,①单独用药组：阿苯达唑组（1μg/ml、10μg/ml）、伊曲康唑组（0.7 mg/ml）、伊维菌素组（1.75 mg/ml）、米替福新组（0.5μg/ml、2.5μg/ml和7.5μg/ml）、硝唑尼特组（0.1μg/ml、1μg/ml和10μg/ml）、利福平组（10μg/ml）;②联合用药组：硝唑尼特联合阿苯达唑10μg/ml＋10μg/ml组、10μg/ml＋1μg/ml组、1μg/ml＋10μg/ml组和1μg/ml＋1μg/ml组;③对照组：二甲基亚砜组（2μl/ml）和空白对照组。培养6周,观察囊泡塌陷情况,对囊泡进行计数,并绘制囊泡曲线。6周后停药,联合用药组连续观察3周、3个月和6个月,观察泡球蚴囊泡生长情况。将各药物组体外培养的泡球蚴接种于雌性BALB/c小鼠,饲养8周后处死并剖检观察小鼠腹腔内有无泡球蚴生长并称重,测试泡球蚴活力。结果伊维菌素、米替福新和利福平对泡球蚴无抑制或杀灭作用。阿苯达唑、伊曲康唑、硝唑尼特,及硝唑尼特与阿苯达唑联合用药在体外均能抑制泡球蚴的生长或杀灭泡球蚴（P〈0.05）,高浓度的硝唑尼特（10μg/ml）更能迅速、有效地发挥作用。硝唑尼特与阿苯达唑以不同的浓度联合用药,停药后分别连续观察3周、3个月和6个月,各组均无泡球蚴囊泡生长。泡球蚴活力测试发现,单独用药组中,除硝唑尼特（10μg/ml）组所有小鼠、阿苯达唑组5只小鼠和联合用药组所有小鼠外,其余各组小鼠的腹腔中均有泡球蚴生长。结论阿苯达唑、伊曲康唑、硝唑尼特体外对泡球蚴均有一定的抑制作用,硝唑尼特和阿苯达唑联合用药可提高抑制效果。
Objective To test the effect of 6 drugs or combination on the in vitro cultured Echinococcus multilocularis（Em）metacestodes.Methods The drugs used included albendazole（ABZ）,itraconazole（ITZ）,ivermectin,miltefosine,nitazoxanide（NTZ）,and rifampin.The Em metacestodes were cultured for 5 weeks and divided into 17 groups each with 120-140 cysts：ABZ groups（1 μg/ml and 10 μg/ml）,ITZ group（0.7 mg/ml）,ivermectin group（1.75 mg/ml）,miltefosine groups（0.5 μg/ml,2.5 μg/ml and 7.5 μg/ml）,NTZ groups（0.1 μg/ml,1 μg/ml and 10 μg/ml） and rifampin group（10 μg/ml）;groups of NTZ combined with ABZ at respective concentration（10 μg/ml ＋10 μg/ml,10 μg/ml＋1 μg/ml,1 μg/ml＋10 μg/ml,1 μg/ml＋1 μg/ml）;and 2 groups of control： ① experiment culture containing 40 μl of dimethyl sulfoxide（DMSO） per 20 ml and ② blank culture medium.In the 6 weeks culture period,the drug effect on the Em cysts was observed.Drug combination groups were continually observed for 3 weeks,3 months and 6 months after discontinuation of drugs.In order to determine the viability of metacestodes,the cysts were injected intraperitoneally into female BALB/c mice,and 8 weeks later,the mice were sacrificed for collecting the parasites.Results Ivermectin,miltefosine and rifampin showed no effect on metacestodes.Albendazole,itraconazole,nitazoxanide and albendazole combined with nitazoxanide all inhibited or killed the parasites in the in vitro culture system（P0.05）.High dose of nitazoxanide（10 μg/ml） was more effective in the destroying parasites than others.No re-growth of cysts was observed in the 4 groups of combination treatment with nitazoxanide and albendazole continually cultured for 3 weeks,3 months,or 6 months after drug discontinuation.In the in vivo viability test,no metacestodes were found in all mice in the nitazoxanide group（10 μg/ml） and 2 mice in albendazole group,but the parasites developed in all mice at 8 weeks after injection in other single drug groups.Also,no met
出处
《中国寄生虫学与寄生虫病杂志》
CAS
CSCD
北大核心
2011年第6期419-424,共6页
Chinese Journal of Parasitology and Parasitic Diseases
基金
国家自然科学基金(No.30760239)~~
