4种药物单用或联用治疗大鼠华支睾吸虫感染的实验研究

目的观察三苯双脒(TBD)、青蒿琥酯(AS)、阿苯达唑(ABZ)、甲苯咪唑(MBZ)单用或联用治疗感染华支睾吸虫大鼠的疗效。方法 140只大鼠各感染华支睾吸虫囊蚴100个,于感染后第5周开始分组治疗,均采用灌胃给药。感染大鼠随机分为药物治疗组同批感染对照组(每组5～10只),将TBD、AS、ABZ与MBZ分别按照高、低剂量单剂用药和两两配伍给药,顿服,观察疗效。治疗后10d处死大鼠,解剖,收集胆管和肝组织内的华支睾吸虫,计算平均虫数和减虫率,对相应组间的平均虫数进行单因素方差分析。结果感染华支睾吸虫大鼠用75mg/kg体重TBD、MBZ、ABZ单剂治疗后,平均减虫率分别为98.04%、100%和86.67%,30mg/kg体重AS治疗后减虫率为87.25%;当给药剂量均降低1/3时,上述各药物治疗组的平均减虫率分别降至78.3%、46.02%、31.94%和62.07%。50mg/kg体重TBD分别与50mg/kg体重MBZ、ABZ配伍用组平均减虫率为98.43%和100%,检虫数与75mg/kg体重TBD、MBZ、ABZ单用药组比较,差异有统计学意义(P<0.05)。20mg/kg体重AS分别与50mg/kg体重ABZ、50mg/kg体重MBZ配伍用,平均减虫率为89.22%和97.55%,检虫数与75mg/kg体重ABZ、MBZ,30mg/kg体重AS单用药组比较,差异有统计学意义(P<0.05)。结论联合用药可降低给药剂量,并具有增效作用,50mg/kg体重TBD分别与50mg/kg体重MBZ、ABI配伍用对治疗大鼠华支睾吸虫病疗效较好。

Effects of single or multiple doses of intragastrically administered tribendimidine,mebendazole,albendazole,and artesunate on rats infected with Clonorchis sinensis

Objective To assess the efficacy of single or combined oral doses of tribendimidine,mebendazole,albendazole,or artesunate on Clonorchis sinensis in rats.Methods One hundred and forty rats were infected with 100 C.sinensis metacercariae and treated with experimental chemotherapy.All drugs were administered intragastrically 5 weeks after infection.Infected rats were randomly divided into drug treatment groups and untreated groups(5 to 10 rats per group).In order to observe the effects of the five drugs on juvenile C.sinensis,tribendimidine,mebendazole,albendazole,and artesunate were used in single or combined oral doses given at relatively high or low doses.All groups except the control groups were given separate doses.Rats were sacrificed 10 days after treatment.Worms were recovered from the bile ducts and the liver tissue of rats,the mean reduction in worm burden was calculated,and the mean worm burden was compared among the groups using one-way ANOVA.Results Rats infected with C.sinensis and treated with a single 75 mg/kg dose of tribendimidine,mebendazole,or albendazole had a high worm reduction of 98.04%,100%,and 86.67%,respectively,while rats treated with 30 mg/kg dose of artesunate had worm reduction of 87.25%.However,a single 50 mg/kg dose of tribendimidine,mebendazole,or albendazole resulted in slightly lower worm reduction of 78.3%,46.02%,and 31.94%,respectively,while a 20 mg/kg dose of artesunate resulted in worm reduction of 62.07%.Results showed that single doses of drugs were more effective at an increased dosage.Combined treatment of 20 mg/kg artesunate plus 50 mg/kg albendazole or 50 mg/kg mebendazole resulted in worm reduction of 89.22% and 97.55%.Combining drugs was significantly more effective than single-dose treatment with 75 mg/kg albendazole or 30mg/kg artesunate but less effective than single-dose treatment with 75 mg/kg mebendazole.Resultssuggested that combining these drugs could both allow their dosage to be reduced and make treatment more effective.Conclusion The investigation confirmed that,compared to single doses,drug combinations act synergistically at lower doses,enhancing the effectiveness of treatment of C.sinensis.Combined treatment of 50 mg/kg tribendimidine plus 50 mg/kg mebendazole or 50 mg/kg albendazole was relatively effective at treating rats infected with this parasite.