氯硝柳胺在小鼠血浆中的代谢及抗日本血吸虫尾蚴侵袭作用  

Plasma Metabolism and Protective Effect of Oral Administration of Niclosamide on Schistosoma japonicum Cercarial Invasion in Mice

作　　者：涂珍[1] 姜斌[1] 薛剑[1] 陶奕[1] 魏玉芬[1] 张皓冰[1] 

机构地区：[1]中国疾病预防控制中心寄生虫病预防控制所卫生部寄生虫病原与媒介生物学重点实验室世界卫生组织疟疾血吸虫病和丝虫病合作中心,上海200025

出　　处：《中国寄生虫学与寄生虫病杂志》2015年第2期101-104,共4页Chinese Journal of Parasitology and Parasitic Diseases

基　　金：国家国际科技合作专项(No.2014DFA31130)~~

摘　　要：目的通过观察氯硝柳胺口服后血药浓度变化,了解药物在小鼠血浆中的代谢情况,并对其抗日本血吸虫尾蚴侵袭的效果进行观察。方法将24只雌性昆明小鼠随机分成8组,每组3只。每鼠灌胃给药0.2 ml/20 g,剂量为120 mg/kg体重。于给药后0.25、0.5、1、2、4、8、16和24 h眼眶采血,收集血浆,采用高效液相色谱法(HPLC)测定不同时间点的血药浓度,计算药峰浓度(Cmax)、达峰时间(Tmax)、平均滞留时间(MRT)和消除半衰期(T1/2)等药代动力学参数。另取30只昆明小鼠,随机分成6组,每组5只,分别灌胃给药40、80、120、160和200 mg/kg,余下1组作为对照组。给药1 h后进行尾蚴攻击感染,每鼠(40±2)条。再取35只昆明小鼠,随机分成7组,每组5只,灌胃给药200 mg/kg,余下1组作为对照组。于给药后0.25、1、4、8、12和24 h进行尾蚴攻击感染,每鼠(40±2)条。各组小鼠均于感染后35 d处死,计数体内血吸虫成虫数,计算减虫率。结果 120 mg/kg氯硝柳胺灌胃给药后0.25 h,小鼠血药浓度即达到(0.40±0.28)μg/ml,1 h时达到最大值(0.91±0.34)μg/ml,到2 h时已降至(0.49±0.38)μg/ml,之后继续下降,16 h后趋近于0;MRT为(6.78±1.47)h,T1/2为(6.80±7.05)h。氯硝柳胺不同剂量组35 d后检获虫数与对照组差异均无统计学意义(P>0.05)。200 mg/kg氯硝柳胺给药后0.25 h进行尾蚴攻击,35 d后检获虫数显著少于对照组(P<0.05),减虫率为79.1%,其他各组与对照组间差异无统计学意义(P>0.05)。结论氯硝柳胺灌胃给药后,血药浓度迅速上升,1 h可达到峰值。200 mg/kg氯硝柳胺给药后0.25 h时对尾蚴侵袭有一定抵抗效果。Objective To study the metabolism of niclosamide in plasma， and the protective effect of its oral administration on Schistosoma japonicum cercarial invasion in mice. Methods Twenty-four female Kunming mice were randomly divided into 8 groups， each with 3 mice. Each mouse was treated orally with 120 mg niclosamide per kilogram of body weight （120 mg/kg）. The plasma samples were collected at 0.25， 0.5， 1， 2， 4， 8， 16， and 24 h after treatment by retro-orbital blood sampling. The blood drug concentration was determined by HPLC. The pharmacokinetics parameters were calculated such as peak concentration（Cmax）， peak time（Tmax）， mean residence time（MRT）， and elimination half life（T1/2）. Thirty Kunming mice were randomly divided into 6 groups. Among them， 5 groups were treated orally with 40， 80， 120， 160， and 200 mg/kg niclosamide， respectively. The remaining untreated group served as control. One hour post-treatment， each mouse was infected with 40±2 Schistosoma japonicum cercariae. Another 35 mice treated with 200 mg/kg niclosamide were randomly divided into 7 groups. Mice in each group were infected with 40±2 S. japonicum cercariae on 0.25， 1， 4， 8， 12， and 24 h after treatment， named as group A， B， C， D， E， and F. Five untreated mice served as control（group G）. All mice were sacrificed 35 days post-infection. Mean worm burden and worm reduction were calculated. Results At a dose of 120 mg/kg niclosamide， the blood drug concentration was （0.40±0.28） μg/ml at 0.25 h post-treatment， reached a peak of （0.91±0.34） μg/ml at 1 h， and decreased to （0.49±0.38） μg/ml at 2 h， and got close to 0 at 16 h. The mean residence time（MRT） in mice was （6.78±1.47） h， and the elimination half time was （6.80±7.05） h. No significant difference was found in worm burden between different dose groups and control group（P＞0.05）. The mean worm burden in group A was significantly lower than that of the control （

关 键 词：氯硝柳胺 小鼠 药代动力学 灌胃 日本血吸虫 尾蚴 

分 类 号：R383.24[医药卫生—医学寄生虫学]