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目的观察三苯双脒、青蒿琥酯、蒿甲醚、或吡喹酮单剂、多剂给药,及其伍用治疗感染华支睾吸虫大鼠的疗效。方法147只SD大鼠各感染50个华支睾吸虫囊蚴,于感染后42～44d分组治疗。各药物采用灌胃给药。①60只感染大鼠随机分为11组(每组4～5只),分别为三苯双脒150mg/kg(顿服)、75mg/(kg·d)×2d、50mg/(kg·d)×3d和25mg/kg(tid)×2d组;吡喹酮150mg/kg(顿服)、75mg/(kg·d)×2d和25mg/kg(tid)×2d;青蒿琥酯或蒿甲醚75mg/kg(顿服)和37.5mg/(kg·d)×2d组。②另87只感染大鼠随机分为15组(每组4～6只),用青蒿琥酯或蒿甲醚(30mg/kg)分别与吡喹酮(150mg/kg)、三苯双脒(50mg/kg和75mg/kg)伍用组;三苯双脒(50mg/kg)与吡喹酮(150mg/kg)伍用组;三苯双脒(75mg/kg)与吡喹酮(187.5mg/kg)伍用组,及各药的单用组。并设同批感染未治疗对照组。受治鼠于治疗后2周剖杀,收集胆管和肝组织内的残留华支睾吸虫,计算各组的平均虫数和减虫率,用非参数统计方法(Mann-Whitney秩和检验)对相应组间的平均虫数进行分析。结果感染华支睾吸虫的大鼠口服单剂三苯双脒或吡喹酮(150mg/kg)的减虫率分别为57.2%和63.8%。三苯双脒各小剂量多次给药组的减虫率稍高,达77.1%～79.4%,而吡喹酮小剂量多次给药组的减虫率则为50.6%～54.2%。但两种药物各组间的平均虫数的差异无统计学意义。青蒿琥酯和蒿甲醚各单剂给药组与小剂量多次给药组的减虫率均较高,分别为90.4%～98.5%和100%。三苯双脒小剂量(50或75mg/kg)与吡喹酮(150mg/kg或187.5mg/kg)伍用治疗,减虫率为74.9%～100%,高于其各单药组的减虫率(26.9%～79.6%)。青蒿琥酯或蒿甲醚小剂量(30mg/kg)与吡喹酮(150mg/kg)或三苯双脒(50或75mg/kg)伍用治疗,减虫率为74.9%～97.9%,亦高于其各药组的减虫率(24.8%～79.6%)。结论青蒿琥酯、蒿甲醚、吡喹酮和三苯双脒均为有效的抗华支睾吸虫药物,各药物小剂量伍用具有增效作用。
Objective To observe the curative effects of tribendimidine, artesunate, artemether, or praziquantel in single dose and multi-dose administration, and their use in treatment of Clonorchis sinensis infection in rats. Methods 147 Sprague - Dawley rats were infected with 50 Clonorchis sinensis metacercariae and treated 42 ~ 44 days after infection respectively. Each drug is administered orally. ①60 infected rats were randomly divided into 11 groups (4 ~ 5 in each group), which were treated with tribendimidine 150mg / kg, 75mg / (kg · d) × 2d, 50mg / (kg · d) Praziquantel 150mg / kg, 75mg / (kg · d) × 2d and 25mg / kg (tid) × 2d; artesunate or artemia Ether 75mg / kg (Dayton) and 37.5mg / (kg · d) × 2d group. ② The other 87 infected rats were randomly divided into 15 groups (4 to 6 in each group), and were treated with artesunate or artemether (30 mg / kg) respectively with praziquantel (150 mg / kg) (50mg / kg) and praziquantel (187.5mg / kg) in the control group. The combination of tribendimidine (50mg / kg) and praziquantel mg / kg) group with Wu, and the drug group alone. And set the same batch infected untreated control group. The treated rats were killed 2 weeks after treatment and the residual Clonorchis sinensis was collected in the bile duct and liver tissues. The average number of worms and the worm reduction rate in each group were calculated. The nonparametric statistical methods (Mann-Whitney rank sum test) The average number of worms among the groups was analyzed. Results The worm reduction rates of single dose of tribendimidine or praziquantel (150 mg / kg) in rats infected with Clonorchis sinensis were 57.2% and 63.8%, respectively. The worm reduction rates for each dose of tribendimidine were slightly higher (77.1% -79.4%) than those for multiple doses of p-benzamidine and 50.6% -54.2% for multiple doses of praziquantel. However, the average number of worms between the two groups of drugs was not statistically different. The worm reduction rates of artesunate and artemether in single-dose and low-dose multiple-dose groups were all higher, ranging from 90.4% to 98.5% and 100% respectively. Tribendimidine (50 or 75 mg / kg) and praziquantel (150 mg / kg or 187.5 mg / kg) were used for combination treatment, and the worm reduction rate was 74.9% -100%, which was higher than that of each single drug group The worm rate (26.9% ~ 79.6%). Artemethrin or artemether with low dose (30mg / kg) and praziquantel (150mg / kg) or tribendimidine (50 or 75mg / kg) Wu treatment, the worm reduction rate was 74.9% to 97.9% Also higher than the worm reduction rate of each group (24.8% ~ 79.6%). Conclusions Artesunate, artemether, praziquantel and tribendimidine are all effective anti-Clonorchis sinensis drugs, and all the drugs have a synergistic effect on small doses.