三苯双脒对华支睾吸虫感染鼠的疗效及其对虫体超微结构的影响

摘要

目的 观察三苯双脒对感染华支睾吸虫仓鼠的疗效及其对华支睾吸虫成虫超微结构的影响. 方法 药效实验:99只仓鼠各感染30条华支睾吸虫囊蚴,分组后灌胃顿服给药治疗,观察各组疗效:1)59只仓鼠于感染后24 d随机分成7组,每组8～9只,分别为三苯双脒50.0、100.0和200.0 mg/kg组,吡喹酮100.0、200.0和300.0 mg/kg组以及对照组；2)40只仓鼠感染后24 d随机分成5组,每组8只,分别为三苯双脒12.5和25.0 mg/kg组,吡喹酮50.0和75.0 mg/kg组以及对照组.各组受治鼠于治疗后2周剖杀,收集胆道系统内的残留华支睾吸虫,计算各组的平均虫数和减虫率.超微结构观察实验:每只大鼠灌胃50条华支睾吸虫囊蚴6周后,分为治疗组和对照组:其中治疗组10只,经三苯双脒300.0mg/kg治疗后,分别于4、8、24、48和72h剖杀大鼠,从胆总管中检获华支睾吸虫；对照组10只,于相同时间点剖杀取虫.检获的华支睾吸虫经处理后,置于透射电镜下观察. 结果 三苯双脒12.5、25.0、50.0、100.0和200.0 mg/kg组的减虫率分别为50.0％、89.7％、95.7％、99.3％和100％,平均虫数与对照组相比差异均有统计学意义.吡喹酮50.0、75.0、100.0、200.0和300.0 mg/kg组的减虫率分别为53.1％、78.6％、81.5％、88.1％和100％.经三苯双脒作用后,大鼠体内华支睾吸虫成虫体壁皮层和皮层细胞内杆状颗粒、盘状颗粒和膜样小泡减少,皮层内线粒体出现空泡,皮层乳突破溃剥落,皮层细胞核变形,核膜消失. 结论 三苯双脒对华支睾吸虫感染鼠有较好疗效,且优于吡喹酮.三苯双脒可引起华支睾吸虫体壁皮层和皮层细胞亚结构破坏.%Objective To observe the efficacy of tribendimidine on hamsters infected with Clonorchis sinensis and the ultrastructural changes of the adult worm after tribendimidine treatment.Methods In the experiment of drug efficacy,a total of 99 hamsters each infected with 30 C.sinensis metacercariae were administrated with tribendimidine and praziquantel to observe the efficacy in following two aspects:1) 59 infected hamsters were randomly divided into 7 groups with 8 or 9 per group at the 24th day after infection:tribendimidine groups of 50.0,100.0,200.0 mg/kg and praziquantel groups of 100.0,200.0,300.0 mg/kg and the control group; 2) 40 infected hamsters were randomly divided into 5 groups:tribendimidine 12.5 and 25.0 mg/kg,praziquantel 50.0 and 75.0 mg/kg and the control group.Each hamster was killed 2 weeks after treatment,C.sinensis was collected from the bile ducts and mean worm burden and mean worm reduction rate were calculated.In the experiment on the ultrastructural changes of adult worm,rats infected with 50 C.sinensis metacercariae were divided into two groups 6 weeks after infection:one group of 10 rats were treated with tribendimidine 300.0 mg/kg and killed at 4,8,24,48 and 72 h after treatment; 10 rats of control group were killed at the same time points.C.sinensis was collected from the bile ducts and observed under transmission electron microscope.Results The worm reduction rates in tribendimidine 12.5,25.0,50.0,100.0 and 200.0 mg/kg group were 50.0％,89.7％,95.7％,99.3％ and 100％ respectively,significant difference was found in mean worm burden compared with that in control group.The worm reduction rates in praziquantel 50.0,75.0,100.0,200.0 and 300.0 mg/kg group were 53.1％,78.6％,81.5％,88.1％ and 100％,respectively.The rod-like granules,disc-like granules and vacuoles in the integument and integument cells of C.sinensis decreased after tribendimidine treatment,and the papillae of integument dissolved and stripped,the vacuolization of mitochondria in the integument appeared,the integument cell nucleus deformed,and parts of cell nuclear membrane dissolved.Conclusions Tribendimidine exhibites good efficacy to hamsters infected with C.sinensis,which is superior to praziquantel.The ultrastructure of integument and integument cells in body of C.sinensis were deformed after tribendimidine treatment.