Meaney M, Allister J, McKinstry B, McLaughlin K, Brennan G P, Forbes A B, Fairweather I
Parasite Proteomics and Therapeutics Research Group, School of Biological Sciences, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK.
Parasitol Res. 2007 Apr;100(5):1091-104. doi: 10.1007/s00436-006-0378-6. Epub 2006 Dec 19.
A study has been carried out to investigate the ultrastructural effects of triclabendazole (TCBZ) at half-normal concentration, clorsulon at half-normal concentration, and a combination of these two drugs against mature Fasciola hepatica. The Cullompton TCBZ-susceptible isolate was used for these experiments. Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 microg/ml), clorsulon (5 microg/ml), or a combination of the two drugs. For the in vivo experiment, rats were dosed with TCBZ (5 mg/kg body weight), clorsulon (5 mg/kg body weight), or a combination of the two drugs, and flukes recovered after 48 h. Fine structural changes within the tegumental syncytium and tegumental cells were assessed by transmission electron microscopy. Treatment with the combination of drugs produced greater disruption to the flukes than the individual drugs at half-normal concentrations, both in vivo and in vitro; also than TCBZ.SO at normal concentration in vitro. The changes observed aid in the understanding of the gross changes to the tegumental surface described previously (Meaney M, Allister J, McKinstry B, McLaughlin K, Brennan GP, Forbes AB, Fairweather I. Parasitol Res 99:609-621, 2006). The results indicate that there are additive effects between TCBZ and clorsulon and suggest that the use of drug combinations would be of value in the treatment of TCBZ-resistant fluke.
开展了一项研究，以调查半正常浓度的三氯苯达唑（TCBZ）、半正常浓度的氯舒隆以及这两种药物联合使用对成熟肝片吸虫的超微结构影响。这些实验使用了对TCBZ敏感的Cullompton分离株。将吸虫在体外于三氯苯达唑亚砜（7.5微克/毫升）、氯舒隆（5微克/毫升）或这两种药物的组合中孵育24小时。对于体内实验，给大鼠分别服用TCBZ（5毫克/千克体重）、氯舒隆（5毫克/千克体重）或这两种药物的组合，48小时后回收吸虫。通过透射电子显微镜评估皮层合胞体和皮层细胞内的细微结构变化。在体内和体外，药物联合治疗对吸虫造成的破坏均比半正常浓度的单一药物更大；在体外也比正常浓度的三氯苯达唑亚砜更大。观察到的这些变化有助于理解先前描述的皮层表面的总体变化（Meaney M、Allister J、McKinstry B、McLaughlin K、Brennan GP、Forbes AB、Fairweather I. Parasitol Res 99:609 - 621, 2006）。结果表明TCBZ和氯舒隆之间存在相加作用，并表明药物联合使用在治疗对TCBZ耐药的吸虫方面具有价值。
