Meaney M, Fairweather I, Brennan G P, Forbes A B
Parasite Proteomics and Therapeutics Research Group, The School of Biology and Biochemistry, The Queen's University of Belfast, BT9 7BL Belfast, Northern Ireland.
Parasitol Res. 2004 Feb;92(3):232-41. doi: 10.1007/s00436-003-1036-x. Epub 2004 Jan 9.
Using transmission electron microscopy (TEM), both the tegument and gut of Fasciola hepatica were examined in an effort to identify and characterise the ultrastructural changes induced following treatment with the flukicidal drug clorsulon. Male Sprague-Dawley rats infected with F. hepatica were dosed orally at 8-8.5 weeks post-infection with clorsulon at a concentration of 12.5 mg/kg body weight. After 24, 48 and 72 h, rats were sacrificed by cervical dislocation and mature flukes recovered from the bile ducts. After 24 h treatment in vivo, disruption of the tegumental syncytium was concentrated at the apex of the syncytium where a dark band consisting of numerous secretory bodies was present. Some blebbing of the apex had also occurred, "open" bodies were present in this region and the mitochondria were slightly swollen. In the cell bodies, swelling of the mitochondria and their cristae had also occurred and the Golgi complexes appeared to be smaller than normal. The disruption seen after 48 h treatment in vivo was similar but more severe: the frequency of blebbing had increased, as had the number of "open" bodies and the swelling of the mitochondria. Vacuoles had begun to appear in the syncytium-both autophagic and electron-lucent-and swelling of the mucopolysaccharide masses around the basal infolds had occurred. Lipid droplets were observed occasionally. In the cell bodies, autophagic vacuoles had begun to appear and swelling of the mitochondria had increased in severity. After 72 h treatment in vivo, more severe disruption was seen in the tegumental syncytium in which widespread swelling and blebbing of the apex was apparent. The basal infolds had become very badly swollen in a number of specimens and damage to the spines was evident. The mitochondria remained swollen, as did the mucopolysaccharide masses around the basal infolds. Lipid droplets were more frequently observed in the syncytium. In the tegumental cells, swelling of the mitochondria was greater and an increase in the number of autophagic vacuoles was apparent. The gut showed signs of disruption after 24 h treatment in vivo, in that the surface lamellae were disrupted and a build-up of autophagic vacuoles at the apex of the cells had taken place. Swelling of the mitochondria and the cisternae of granular endoplasmic reticulum (gER) was evident. There was a decrease in the number of secretory bodies. After 48 h treatment in vivo, the number of autophagic vacuoles in the gastrodermal cells had increased, the mitochondria and gER remained swollen and the disruption seen to the lamellae was still evident. In the 72 h-treated specimens, the disruption seen in the gastrodermal cells had increased significantly, with severe vacuolation of the apical cytoplasm. An increase in the number of autophagic vacuoles was evident, the mitochondria and the gER remained swollen and lipid droplets were present in the cells.
利用透射电子显微镜（TEM），对肝片吸虫的皮层和肠道进行了检查，旨在识别和表征使用杀吸虫药物氯磺隆治疗后诱导的超微结构变化。将感染肝片吸虫的雄性Sprague-Dawley大鼠在感染后8 - 8.5周口服给予浓度为12.5 mg/kg体重的氯磺隆。在24、48和72小时后，通过颈椎脱臼处死大鼠，并从胆管中回收成熟的吸虫。体内治疗24小时后，皮层合胞体的破坏集中在合胞体顶端，此处存在由大量分泌小体组成的暗带。顶端也出现了一些泡状突起，该区域存在“开放”小体，线粒体略有肿胀。在细胞体中，线粒体及其嵴也发生了肿胀，高尔基体似乎比正常情况下小。体内治疗48小时后观察到的破坏情况类似但更严重：泡状突起的频率增加，“开放”小体的数量以及线粒体的肿胀也增加。合胞体中开始出现空泡——自噬空泡和电子透明空泡——并且基底褶皱周围的粘多糖团块发生了肿胀。偶尔观察到脂滴。在细胞体中，自噬空泡开始出现，线粒体的肿胀程度加剧。体内治疗72小时后，皮层合胞体出现更严重的破坏，顶端广泛肿胀和泡状突起明显。在一些标本中，基底褶皱严重肿胀，棘的损伤明显。线粒体仍然肿胀，基底褶皱周围的粘多糖团块也是如此。在合胞体中更频繁地观察到脂滴。在皮层细胞中，线粒体肿胀更严重，自噬空泡数量增加明显。体内治疗24小时后，肠道出现破坏迹象，即表面薄片被破坏，细胞顶端积累了自噬空泡。线粒体和颗粒内质网（gER）的池肿胀明显。分泌小体数量减少。体内治疗48小时后，胃皮细胞中的自噬空泡数量增加，线粒体和gER仍然肿胀，薄片的破坏仍然明显。在72小时治疗的标本中，胃皮细胞中的破坏明显增加，顶端细胞质出现严重空泡化。自噬空泡数量增加明显，线粒体和gER仍然肿胀，细胞中存在脂滴。
