Parasite Therapeutics Research Group, School of Biological Sciences, The Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom.
Vet Parasitol. 2010 Dec 15;174(3-4):218-27. doi: 10.1016/j.vetpar.2010.09.008. Epub 2010 Sep 16.
Eight indoor-reared cross-bred sheep with no pre-exposure to Fasciola hepatica were infected by oral gavage with 200 metacercarial cysts of the triclabendazole (TCBZ)-susceptible Cullompton isolate of F. hepatica. At 12 weeks post-infection, sheep were dosed with 10mg/kg triclabendazole. Two sheep per time period were euthanized at 48 h, 72 h and 96 h post-treatment (pt). Two control sheep were euthanized alongside the 96 h triclabendazole-treated sheep. Flukes were recovered from each of the sheeps liver and, if present, from the gall bladder and they were processed for transmission electron microscopy (TEM). Disruption to the ultrastructure of the tegument became increasingly severe over time pt. Flukes recovered at 48 h pt showed widespread blebbing of the apical plasma membrane and swelling of the mucopolysaccharide masses surrounding the basal infolds. There was evidence of reduced secretory activity in the tegumental cells and spacing between the cells. Sloughing of the tegumental syncytium was observed at 72 h pt. The subtegumental musculature, parenchyma and tegumental cells were severely disrupted. At 96 h pt, all of the flukes were totally devoid of tegument. Disruption to the subtegumental tissue and somatic musculature was severe, and was so extreme in some specimens that the tegumental cells were barely discernible. Disruption to the gastrodermis was also progressive, though not as severe as disruption to the tegument. There was a general decline of secretory activity with time pt. Autophagic activity was apparent from 48 h pt and became more widespread with increasing time, culminating in breakdown of the gastrodermal cell cytoplasm. The mitochondria were swollen and electron-lucent and the cisternae of the granular endoplasmic reticulum were dilated and fragmented from 72 h pt.
八只未曾接触过肝片吸虫的室内饲养杂交绵羊，通过口服灌胃感染了 200 个对三氯苯达唑（TCBZ）敏感的 Cullompton 分离株的囊蚴。感染后 12 周，绵羊用 10mg/kg 的三氯苯达唑进行治疗。在治疗后 48 小时、72 小时和 96 小时，每个时间点处死两只绵羊。与 96 小时三氯苯达唑治疗的绵羊一起，处死了两只对照绵羊。从每只绵羊的肝脏中回收了吸虫，如果存在的话，还从胆囊中回收了吸虫，并对其进行了透射电子显微镜（TEM）处理。随着时间的推移，在治疗后，虫体的超微结构破坏越来越严重。在治疗后 48 小时，吸虫的顶膜广泛起泡，围绕基内褶的粘多糖体肿胀。在表皮细胞中，细胞间的分泌活动减少，细胞间的距离增大。在治疗后 72 小时，观察到表皮的脱屑。在 96 小时，所有的吸虫都完全没有表皮。下表皮肌肉组织、实质组织和表皮细胞受到严重破坏。在治疗后 96 小时，所有的吸虫都完全没有表皮。下表皮组织和体壁肌肉受到严重破坏，在一些标本中，这种破坏非常严重，以至于几乎无法辨认表皮细胞。胃皮层的破坏也在逐渐加重，尽管不如表皮的破坏严重。随着时间的推移，分泌活动普遍下降。自治疗后 48 小时开始出现自噬活性，随着时间的推移，自噬活性变得更加广泛，最终导致胃皮层细胞质的破裂。线粒体肿胀、电子透明，从治疗后 72 小时开始，颗粒内质网的小管和小泡扩张和碎片化。
