细胞松弛素D与钙通道阻滞剂拮抗吡喹酮作用对血吸虫超微结构的影响  

Effect of cytochalasin D and calcium channel blockers on ultrastructure of Schistosoma japonicum treated with praziquantel in vitro

作　　者：蔡茹[1,2] 杨巧林[1] 张惠琴[1] 夏超明[1] 

机构地区：[1]苏州大学医学部基础医学与生物科学学院病原生物学系,苏州215123 [2]安徽理工大学医学院病原生物学教研室,淮南232001

出　　处：《中国人兽共患病学报》2010年第4期315-319,共5页Chinese Journal of Zoonoses

基　　金：卫生部寄生虫病预防与控制重点实验室开放课题(No.WK008-001)资助

摘　　要：目的通过观察细胞松弛素D(cytochalasin D,CyD)与钙通道阻滞剂(calcium channel blockers,CCBs)拮抗吡喹酮(praziquantel,PZQ)体外杀日本血吸虫效应的虫体体表超微结构变化,探讨PZQ对血吸虫的药物靶点及作用机制。方法在日本血吸虫(Schistosoma japonicum,Sj)单性尾蚴感染昆明小鼠6w后,采用门静脉灌注法收集雄性成虫,体外培养。将虫体分别与CyD及CCBs预孵育1h,然后在培养液内加入临界致死剂量的PZQ(14μmol/L)孵育过夜(16h)。次晨,洗涤、更换培养液,继续培养48h收集虫体作扫描电镜观察。结果超微结构显示,经CyD拮抗PZQ复活后虫体皮层无损害,抱雌沟内壁轻微改变。CCBs组尼群地平和尼非地平拮抗PZQ复活虫体,皮层及抱雌沟内壁仅有轻度损伤。结论CyD与CCBs组尼群地平和尼非地平均可拮抗PZQ对日本血吸虫体表超微结构的损伤效应,提示PZQ对虫体体表的损伤并非药物直接作用所致,而是PZQ作用于血吸虫钙通道诱导虫体痉挛性麻痹后的继发效应,实验结果进一步证明了PZQ抗血吸虫的药物靶点可能与血吸虫的钙通道有关。The aim of this study was to observe the scanning electron microscope （SEM） morphological changes of Schistosoma japonicum （S. japonicum） treated with praziquantel （PZQ） whose function was blocked by cytochalasin D （CyD） and calcium channel blockers （CCBs）, in order to explore the mechanism and target of the PZQ activity on S. japonicum. After six weeks of infection with S. japonicum single-sex cercariae, adult male worms were collected by portal vein perfusion from Kunming mice and cultured in vitro. By exposing to CyD and CCBs for 1 hour respectively, the worms were soaked into medium with PZQ at critical concentration of 14 μmol/L for 16 hours. In the next morning, the parasites were washed and soaked in drug-free medium for another 48 hours then observed by SEM. Results showed that there was no damage to the tegument surface of S. japonicum pre-exposed to CyD and survived in critical concentration PZQ, but there were slight changes in the inner wall of gynecophoral canal. Minor injury was observed in tegument surface and gynecophoral canal of the worms which pre-exposed to nitrendipine or nifedipine and survived in critical concentration PZQ. This study showed that the ultrastructural damages of S. japonicum induced by PZQ could be inhibited by CyD, nitrendipine and nifedipine, which suggested that these damages might be associated with the secondary effects of spastic paralysis produced by PZQ instead of a direct effect of PZQ activity in schistosomes. Moreover, the calcium channels of schistosomes may be involved in the mechanism of PZQ activity.

关 键 词：日本血吸虫 吡喹酮 细胞松弛素D 钙通道阻滞剂 超微结构 

分 类 号：R383.24[医药卫生—医学寄生虫学]