OZ78单剂口服治疗对小鼠体内日本血吸虫成虫超微结构的损害(英文)

Ultrastructural Alterations of Adult Schistosoma japonicum Harbored in Mice Treated with a Single Oral Dose of OZ78

目的观察合成的螺金刚烷臭氧化物0278对日本血吸虫成虫所引起的超微结构变化。方法10只小鼠每鼠感染40-60条日本血吸虫尾蚴，感染后35d，取8只小鼠，每鼠口服单剂0278400mg／kg，治后24h、3d、7d和14d各剖杀2只小鼠，用灌注法收集血吸虫，并按常规方法固定和处置虫体，透射电镜观察。从另2只未治疗的感染小鼠体内取虫作对照。结果感染鼠经0278治后24h，雌、雄虫皮层的明显变化是因细胞质突起肿胀致使体表平坦、远端细胞质突起不规则膨大伴有杆状和盘状分泌体减少、皮层基质局灶性溶解、一些细胞质突起融合成大片状、基底膜破裂或消失，感觉器内部结构受损。在皮层下，肌束无或呈轻度肿胀，并查见肌束局灶性溶解，而肌层下的皮层细胞示核肿大、部分核膜模糊和染色质局灶性溶解形成小空泡，在核周胞质内出现变性线粒体。实质组织的主要变化是线粒体变性，以及一些小空泡与髓鞘样结构的形成。肠上皮细胞的明显变化是细胞核的不规则肿大、核仁轻度溶解和部分双层核膜融合、细胞质中的线粒体变性和微绒毛破溃。此时雌虫卵黄细胞最明显的变化为许多卵黄滴破裂，卯黄球释出，继而溶解和融合。治后3～7d，虫体受损的范围和程度加重。雄虫和雌虫的明显损害是细胞质突起的融合、受损细胞质突起剥落或破溃以致肌束显露、感觉器和皮层细胞的严重破坏、肌束局灶性或广泛肿胀和溶解、出现一些大片变性的实质组织和严重受损的肠上皮细胞。雌虫的卯黄细胞则示卵黄滴减少、细胞核局灶性溶解及卵黄细胞间实质组织的广泛溶解。经0278治后14d，存活雌、雄虫的受损皮层和皮层下组织均有一些恢复，而大多数肠上皮细胞和卵黄细胞仍示有明显损害。结论0278对日本血吸虫成虫的皮层和皮层下组织，包括皮层细胞、实质组织、肠上皮细胞和卯黄细胞具有广泛的损害作用。

Objective To observe the nltrastructural alterations of adult Schistosoma japonicum induced by syn- thetic trioxolane OZ78. Methods Eight out of ten mice infected with 40-60 S.japonicum cercariae for 35 d were treat- ed orally with OZ78 at a single dose of 400 mg/kg. Four groups of two mice were killed at 24 h, 3 d, 7 d, and 14 d post treatment, and schistosomes were recovered by perfusion technique, fixed, and examined by transmission electron mi- croscopy. Schistosomes obtained from the remaining two untreated mice served as control. Results After infected mice were treated with OZ78 for 24 h, the prominent alterations in tegument of both male and female worms were observed, which revealed in flattened surface due to swelling of cytoplasmic processes, irregular expansion in distal end of cyto- plasmic processes accompanied by decrease in rod-like and discoid-like secretory bodies, focal lysis of tegumental matrix; fusion of some cytoplasmic processes to form a large piece, disruption or disappearance of basal membrane, and destruc- tion of internal structures in sensory organelles. In the subtegument, no or slight swelling and focal lysis of muscle bun- dles were seen, while the syncytium beneath the muscle showed enlargement of nucleus with indistinction of partial nu- clear membrane, formation of small vacuoles due to focal lysis of chromatin, and emergence of degenerated mitochondria in perinuclear cytoplasm. As to parenchymal tissues, the major alterations included degeneration of mitochondria, forma- tion of some small vacuoles and myelin-like structures. In gut epithelial cells, the prominent alterations were irregular enlargement of nucleus with light lysis of nucleoli and fusion of partial bi-layer nuclear membrane, degeneration of mito- chondria in cytoplasm and collapse of microvilli. At this time point, in the vitelline cells of female worms, the most sig- nificant alteration was the collapse of many vitelline droplets, which led to release of the vitelline balls, followed by their lysis and fusion. Three to 7 d post treatment, the damage to the worms aggravated either in extent or in severity along with time. The significant damages to male and female worms were fusion of cytoplasmic processes, peeling or collapse of damaged cytoplasmic processes resulting in exposure of muscle bundles, severe destruction of sensory organelles and syn- cytium, focal or extensive swelling and lysis of muscle bundles, emergence of some larger piece of degenerated parenchy- real tissues and severe damage to the gut epithelial cell. While in the vitelline cells of female worms, decrease in the number of vitelline droplet, focal lysis of nucleus and extensive lysis of parenchymal tissues among the vitelline cells were also observed. Fourteen days post OZ78 dosing, male and female worms which survived the treatment showed some renovation in damaged tegument and subtegument, while most gut epithelial cells and vitelline ceils still revealed in prominent injury. Conclusion The results demonstrate that OZ78 possesses an extensive damage to the ultrastructure in tegument and subtegument tissues including syncytium, parenchymal tissues, gut epithelial cells, and vitelline cells of adult S. iaponicum.