环孢素A体外抗曼氏血吸虫雄虫的时间生物学研究

目的：探讨环孢素Ａ体外抗曼氏血吸虫的作用。方法：ＭＦ１小鼠实验感染曼氏血吸虫６ｗｋ后，经主动脉和门静脉灌注收虫。将雄虫放入含有１μｇ／ｍｌ、１０μｇ／ｍｌ、１５μｇ／ｍｌ、２０μｇ／ｍｌ和２５μｇ／ｍｌ环孢素Ａ的１９９培养液中体外培养。用扫描电镜对药物所致的虫体皮层损害作时间生物学观察。结果：在体外，雄虫经１μｇ／ｍｌ环孢素Ａ作用后，体嵴的结构疏松；经１０μｇ／ｍｌ环孢素Ａ作用２４ｈ后，雄虫皮层肿胀；雄虫经１５μｇ／ｍｌ环孢素Ａ作用８ｈ－２４ｈ后，虫体皮层破溃；虫体经２０μｇ／ｍｌ药物作用２４ｈ后，雄虫皮层明显破溃；雄虫经２５μｇ／ｍｌ环孢素Ａ作用８ｈ后，皮层褶嵴受损；作用１６ｈ后，皮层肿胀；作用２４ｈ后，皮层极度破溃，皮棘脱落。药物所致的虫体皮层损害与剂量和时间呈依赖关系。结论：环孢素Ａ具有直接杀曼氏血吸虫的作用。     

环孢素A对体外培养的曼氏血吸虫雌虫超微结构的影响

ＭＦ１小鼠人工感染曼氏血吸虫六周后，经主动脉和门静脉灌注收虫。雌虫暴露在含有不同剂量环抱素Ａ的１９９培养液中体外培养。２４小时后，经药物作用后的虫体分别作扫描电镜和透射电镜观察。雌虫体表嵴结构肿胀；外皮层基质出现空泡；卵黄细胞崩解、卵黄球减少；肠上皮细胞破坏，微绒毛缺损。本结果表明，环孢素Ａ对曼氏血吸虫雌虫具有直接作用，虫体外皮层、卵黄细胞和肠上皮似乎是药物攻击的靶结构。     

环孢素A体外抗AF18标记的曼氏血吸虫童虫的作用

目的探讨环孢素A抗曼氏血吸虫童虫的作用机制。方法制备童虫,环孢素A体外作用,AF18标记,荧光显微镜观察;定量童虫荧光素的分布以及测定光漂洗后童虫荧光素的复原率。结果童虫损伤或死亡,虫体逐渐从绿色变成黄色,虫体表面损伤;随着环孢素A剂量加大,童虫荧光素定量增加;童虫光漂洗后荧光素的复原率大幅度降低。结论环孢素A增加童虫AF18的含量,降低童虫荧光素的复原率,减低童虫表膜流动性;提示,表膜是药物作用的靶标。     

环孢素A体外抗曼氏血吸虫作用的观察

ＭＦ１小鼠实验感染曼氏血吸虫尾蚴１周、３周和６周后，分别经肺静脉和门静脉灌注取虫。实验显示，药物体外抗曼氏血吸虫的作用呈时间、剂量和虫龄依赖方式，童虫和雄虫对药物更敏感。     

环孢素A体外抗FITC-ConA标记的曼氏血吸虫童虫的作用

目的 探讨环孢素A体外抗FITC—ConA标记的曼氏血吸虫童虫的作用以及虫体表膜通透性。方法 人工制备曼氏血吸虫童虫，使用FITC—ConA进行标记，环孢素A体外作用，荧光显微镜下观察并摄照。结果 童虫损伤或死亡，虫体逐渐从淡蓝色变成亮蓝色，虫体可见多个亮蓝色小点，虫体表面损伤。结论 环孢素A能增加童虫表膜流动性。     

环孢菌素A体外抗曼氏血吸虫的透射电镜观察

ＭＦ１小鼠实验感染曼氏血吸虫６ｗｋ后，经主动脉和门静脉灌注收虫。虫体暴露在含有２５μｇ／ｍｌ环孢菌Ａ的１９９型培养液中体外培养。药物所致的虫体损害作透射电镜观察。结果表明，雄虫较雌虫体外对环孢菌素Ａ更敏感，药物作用８ｈ后，雌虫皮质基层有空泡形成；药物作用１６ｈ后，雌虫外质膜破溃、皮棘松动；药物作用２４ｈ后，雌虫实质中有空泡形成、卵黄腺细胞破坏、卵黄小滴减少，雄虫基质有巨大空泡形成、皮棘缺损。结果显     

环孢素A体外抗AF18标记的曼氏血吸虫童虫的研究

目的　探讨环孢素A体外抗AF18标记的曼氏血吸虫童虫的作用以及虫体表膜流动性。　方法　制备童虫,环孢素A体外作用,AF18标记,荧光显微镜观察。　结果　童虫损伤或死亡,虫体逐渐从绿色变成黄色,虫体表面损伤。　结论　环孢素A增加童虫AF18的含量,减低童虫表膜流动性。     

环孢菌素A体外抗曼氏血吸虫的透射电镜观察

ＭＦ１小鼠实验感染曼氏血吸虫６ｗｋ后，经主动脉和门静脉灌注收虫。虫体暴露在含有２５μｇ／ｍｌ环孢菌素Ａ的１９９型培养液中体外培养。药物所致的虫体损害作透射电镜观察。结果表明，雄虫较雌虫体外对环孢菌素Ａ更敏感，药物作用８ｈ后，雌虫皮质基层有空泡形成；药物作用１６ｈ后，雌虫外质膜破溃、皮棘松动；药物作用２４ｈ后，雌虫实质中有空泡形成、卵黄腺细胞破坏、卵黄小滴减少，雄虫基质有巨大空泡形成、皮棘缺损。结果显示，环孢菌素Ａ具有直接杀虫作用，外皮质似乎是药物首先攻击的靶结构，而２５μｇ／ｍｌ环孢菌素Ａ是较理想的作用剂量     

环孢素A体外抗AF18标记的曼氏血吸虫童虫的研究

目的探讨环孢素A体外抗AF18标记的曼氏血吸虫童虫的作用以及虫体表膜流动性。方法制备童虫，环孢素A体外作用，AF18标记，荧光显微镜观察。结果童虫损伤或死亡，虫体逐渐从绿色变成黄色，虫体表面损伤。结论环孢素A增加童虫AF18的含量，减低童虫表膜流动性?     

环孢素A及其衍生物FK506体内抗长爪沙鼠日本血吸虫病的研究

目的本文报告了曼氏血吸虫有明显杀虫效果的环孢素A及其衍生物FK506对长爪沙鼠日本血吸虫病保护作用的初步研究。结果显示,环孢素A对长爪沙鼠日本血吸虫病有明显的保护作用,减虫率为41.62%;减卵率为72.91%;经环孢素A作用后,日本血吸虫虫体表面出现肿胀、水泡、破损、感觉乳突变形或消失等改变;而FK506则几乎没有作用,减虫率仅4.99%;减卵率仅6.39%;经FK506处理后,与对照组相比,虫体活力和皮层无明显变化。环孢素A与FK506两者间的杀虫区别值得进一步探讨。     

血吸虫对吡喹酮抗药性的研究Ⅴ吡喹酮对曼氏血吸虫吡喹酮抗性株和敏感株成虫皮层的损伤

目的 体内比较吡喹酮对曼氏血吸虫吡喹酮抗性株与敏感株成虫皮层的损伤程度。方法 用各虫株尾蚴分别感染小鼠,感染后第57天,以300mg/kg微粒化吡喹酮悬液对小鼠作灌胃治疗;在灌药后10、30min和1、12、24h后剖杀感染小鼠,门静脉灌注收集成虫,按常规方法制成扫描电镜标本,扫描电镜下观察成虫体表的变化。结果 吡喹酮诱导的皮层损伤主要为虫体表形成泡状结构的薄壁隆起;给药10min,敏感株雄虫皮层可见较多小泡状物,而抗性株则少见;1h后,敏感株虫体表可见大量的泡状物,泡状物溃破可形成皮层损伤灶,抗性株仅见少量的泡状物;24h后,敏感株雄虫体表完全受损,部分皮层剥落,暴露出肌肉层,而抗性株仅见少量泡状物和破损的泡状物。给药1h后,敏感株雌虫开始出现少量泡状物,抗性株雌虫体表未见泡状损伤;12h后,敏感株雌虫泡状物数量增加,抗性株仅在有限区域见少量泡状物。结论 抗性株和敏感株成虫体表吡喹酮诱导的皮层损伤程度存在明显差异,敏感株的损伤程度重于抗性株,雄虫重于雌虫。     

Tegumental changes in 21-day-old Schistosoma mansoni harboured in mice treated with artemether

Alterations in the tegument of 21-day-old Schistosoma mansoni, caused by artemether administered to the infected mice, were studied using scanning electron microscopy (SEM). Mice were infected with S. mansoni cercariae, and after 21 days a single dose of artemether (400 mg/kg) was administered intragastrically. After 24, 72 h and 7 days groups of three mice were killed and the schistosomules collected by perfusion, fixed and processed routinely, and examined by SEM. After 24 h, all male and female worms examined showed alterations in the tegument, characterised by swelling, vesiculation and fusion of tegumental ridges; peeling, erosion and collapse of damaged tegumental surface, and also destruction of the oral sucker and acetabulum. After 72 h, severe damage to the tegument was seen, usually including extensive peeling, swelling and vesiculation, and host leukocytes were adhered to the damaged surface. Some worms were surrounded by clusters of host leukocytes or had even disintegrated. Seven days after treatment, some schistosomules still showed severe tegumental damage, but in some cases the damage was less than at earlier times, which suggested that those schistosomules that had survived were beginning to recover. The ability of artemether to cause severe damage to the tegument correlates with its high efficacy in killing 21-day-old schistosomules.     

Schistosoma japonicum and S. mansoni: ultrastructural damage in the tegument and reproductive organs after treatment with levo- and dextro-praziquantel

Ultrastructural observations were made of changes in the tegument and reproductive organs of Schistosoma japonicum and S. mansoni from ICR mice after treatment with praziquantel (PZQ), levo-PZQ, and dextro-PZQ at a single oral dose of 500 mg/kg body weight. No marked difference in types and extent of lesions of the tegument of S. japonicum was found between the compounds regardless of the time of worm recovery after treatment. This was equally true of S. mansoni. Degeneration of the testis, ovary, and vitelline gland of S. japonicum was more prominent in worms administered PZQ and levo-PZQ than in those receiving dextro-PZQ. In S. mansoni, extensive regression of the reproductive organs was observed in male and female worms treated with PZQ and dextro-PZQ, while no serious damage was seen in worms treated with levo-PZQ.     

Synergistic action of cyclosporin A and polyspecific rabbit anti-sera against murine Schistosoma mansoni

The efficacy of cyclosporin A (CsA) treatment against Schistosoma mansoni in mice was compared with treatments that included co-administration of one of two anti-sera (infected rabbit serum (IRS) obtained by repeated infection and a worm membrane antigen anti-serum (WSS) obtained by immunization with worm surface supernatants). These two sera recognized a number of worm antigens but differed in precise detail. Administration of CsA alone to mice harbouring mature infections of S. mansoni reduced worm burdens and preferentially targeted female worms. Sera administered alone had no effect on worm burdens. Co-administration of worm membrane antigen anti-serum (WSS) with CsA reduced worm burden significantly compared with drug treatment alone. Male worms were more susceptible to this combined treatment regime. Anti-infection serum (IRS) had a lesser stimulatory activity in combination with CsA which was not statistically different from the effects of CsA alone on worm burdens. The data suggest that CsA-induced surface damage to the parasite may reveal specific antigens that were previously unavailable for host attack.     

Tegumental changes in adult Schistosoma mansoni harboured in mice treated with praziquantel enantiomers

Praziquantel administered to the host causes damage to the tegument of Schistosoma mansoni. In this study, the effects of racemic praziquantel (Pra) and its enantiomers, levo-praziquantel (L-Pra) and dextro-praziquantel (D-Pra) were compared using scanning electron microscopy (SEM). Mice infected with S. mansoni for 49 days were treated with a single dose of Pra (300 mg/kg), L-Pra (150 mg/kg) or D-Pra (150 or 600 mg/kg). Groups of three mice were killed after 4 and 24 h, and schistosomes collected by perfusion and examined by SEM. Treatment with Pra or L-Pra, for 4 or 24 h, caused tegumental damage to S. mansoni including severe swelling, vacuolization, fusion of the tegumental ridges and loss or shortening of the spines on the tubercles, collapse and peeling. After treatment with D-Pra at 150 mg/kg, no apparent damage was observed. When the dosage was increased to 600 mg/kg, after 4 h lesions on the tegument similar to those induced by Pra or L-Pra were seen, but less severe. After 24 h, there was evidence of recovery. The study thus clearly showed that L-Pra was more active than D-Pra in causing tegumental damage. D-Pra showed a qualitatively similar activity at a higher concentration. It is possible that this effect was due at least to some extent to the small amount of L-Pra (<2%) which was present in the preparation of D-Pra used.     

Enzyme immunoassay of the level of parasite-specific IgE antibodies in schistosomiasis using the monoclonal antibody BL-IgE 9

Sera from patients with chronic schistosomiasis (Schistosoma mansoni or Schistosoma haematobium) were examined for the presence of parasite specific IgE antibodies by means of ELISA technique using tegument antigen prepared from adult worms of Schistosoma mansoni and using the monoclonal antibody BL-IgE 9. Individuals from tropical countries who had no schistosomiasis and blood donors from GDR were studied for comparison. Significantly higher levels of specific IgE antibody were given by sera from patients with schistosomiasis than by the controls. These differential responses serologically differentiated between patients with chronic schistosome infections and noninfected individuals.     

蒿甲醚对感染小鼠体内埃及血吸虫超微结构的影响

目的 观察蒿甲醚对小鼠体内埃及血吸虫成虫超微结构的损害。 方法 8只小鼠于感染埃及血吸虫尾蚴后81 d用单剂蒿甲醚400 mg/kg口服治疗。治后24 h、3 d、7 d和14 d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，作透射电镜观察。从另2只未治疗的感染小鼠体内取虫作对照。 结果 蒿甲醚对血吸虫皮层超微结构的损害主要是皮层基质的肿胀、溶解和空泡变化，基底膜消失和部份受损皮层破裂；在感觉器和皮层结节中，常见其内部结构广泛溶解。在肌层、实质组织、合体细胞和肠管上皮细胞中，查见局灶性或广泛的溶解、粗面内质网减少及线粒体空泡变化和变性。雌虫卵黄细胞的严重变化是空泡变化、粗面内质网减少、卵黄球融合以及受损卵黄细胞破溃等。上述雌、雄虫变化于感染小鼠用蒿甲醚治疗后24 h即可见到，并逐渐加重，3~7 d后最重。治后14 d，部分雌、雄虫仍示有超微结构的损害，但同时亦观察到受损虫组织的恢复。 结论 蒿甲醚对埃及血吸虫成虫的皮层和皮层下组织具有广泛和严重的超微结构损害。