蒿甲醚对日本血吸虫超微结构的影响

目的：了解蒿甲醚对日本血吸虫超微结构的影响。方法：小鼠于感染日本血吸虫尾蚴后７或３５ｄ灌服蒿甲醚２００ｍｇ·ｋｇ－１·ｄ－１，连给２ｄ，并于治后１、３、７、１４和２８ｄ剖检取虫体作透射电镜观察。结果：治后１－７ｄ，在虫的皮层、合体细胞、肌束、实质组织、肠管上皮细胞和卵黄细胞等均发现超微结构变化。主要的损害为皮层基质模糊、疏松、溶解和空泡形成；皮层细胞质突起的外质膜模糊、融合、电子密度增加和破溃，以及感觉结构的变性等。皮层下的肌束、合体细胞和肠管上皮细胞可查见广泛的肿胀、溶解和空泡形成。雌虫的卵黄细胞亦示有核空泡变化、粗面内质网减少和卵黄球溶解等。治后１４－２８ｄ，一些存活虫的超微结构变化已恢复，但有的虫仍示有损害。结论：蒿甲醚对７ｄ童虫和３５ｄ成虫的超微结构均有明显影响。     

蒿甲醚对感染小鼠体内埃及血吸虫皮层的损害

目的 评价蒿甲醚对小鼠体内埃及血吸虫皮层的损害作用。 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。治疗后1、3、7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，作扫描电镜观察。从另2只未作治疗的感染小鼠取虫作对照。 结果 用蒿甲醚治疗后24 h，雄虫的皮层结节肿大、破溃或从皮层上剥落; 在雄虫和雌虫的体表可查见有局灶性或广泛的皮层肿胀、融合、空泡变化、糜烂和剥落，以及感觉结构的破坏。治疗后3 d，雌、雄虫的皮层损害加重，最严重的损害为口吸盘肿胀和破溃，并查见皮层褶嵴有广泛和严重的肿胀、糜烂和剥落，以及雌虫盘状感觉结构的破坏。治疗后7至14 d，有些虫仍示有中或重度皮层损害，而有些仍存活的虫则示其大部分皮层已有明显恢复。 结论 蒿甲醚对埃及血吸虫的皮层具有广泛和严重的损害作用。     

蒿甲醚对曼氏血吸虫的作用:剂量与效应的关系和虫的形态学和组织病理学的变化

目的　应用感染曼氏血吸虫 (利比里亚株 )的小鼠观察蒿甲醚单剂量与效应的关系,虫体肝移及蒿甲醚所引起的虫的形态学和组织病理学变化。　方法　感染21d童虫的小鼠一次口服蒿甲醚12.5mg/kg至600mg/kg不同剂量 ,治后28d剖检观察各组虫数。感染46d或70d成虫的小鼠一次口服蒿甲醚40 0mg/kg后8～14d ,观察虫体肝移及其形态和组织病理学变化。　结果　蒿甲醚对21d童虫的最低有效剂量为200mg/kg ,减虫率为 81%。用蒿甲醚治疗后8h成虫开始肝移,3～7d全部肝移,14d有31%的虫返回肠系膜静脉。成虫虫体萎缩,咽部扩大,肠管膨胀及其色素减少。雌虫局部体表受损,白细胞附着,卵巢及卵黄腺变性退化,以及雄虫睾丸萎缩等。在肝内的虫体被嗜酸粒细胞为主的炎细胞包围和浸润。　结论　蒿甲醚对小鼠曼氏血吸虫21d童虫的最低有效剂量为200mg/kg ,可引起曼氏血吸虫成虫萎缩、退化或死亡。在肝内受损的虫体主要是被嗜酸粒细胞包围和侵袭所致。     

蒿甲醚对血吸虫超微结构的影响

蒿甲醚是青蒿素的一个衍生物,不仅是有效的抗疟药,而且对血吸虫特别是血吸虫童虫亦有效,并已在20世纪末被发展为预防血吸虫病的药物.为了了解蒿甲醚的抗血吸虫作用,除观察其对血吸虫生化代谢的影响外,还用扫描电镜和透射电镜观察了蒿甲醚对感染人体的主要3种血吸虫,即日本血吸虫、曼氏血吸虫和埃及血吸虫超微结构的影响,结果表明蒿甲醚不仅损害血吸虫的皮层、感觉器和皮层结节,而且对虫的肌层、实质组织、肠上皮细胞和卵黄细胞等亦引起广泛的损害.该文综述了蒿甲醚对这3种血吸虫超微结构损害的观察结果,并进行了讨论.     

甲氟喹单剂口服治疗对小鼠体内日本血吸虫成虫皮层的损害(英文)

目的观察甲氟喹对感染小鼠体内日本血吸虫成虫皮层的损害。方法12只雌性昆明小鼠每鼠感染60～80条日本血吸虫尾蚴,其中10只小鼠于感染后35d用甲氟喹单剂400mg/kg口服治疗,治疗后8h、24h、3d、7d和14d分别剖杀2只,用灌注法收集血吸虫,常规方法固定、逐级乙醇脱水和临界点干燥器干燥,用扫描电镜观察,另2只未治疗的感染小鼠取虫作对照。结果甲氟喹给药后8h,雌、雄虫即示虫体局部肿大,有广泛的皮层褶嵴肿胀、紧密接触和融合,并有少数感觉结构(sensory structure)肿大或部分有破溃。给药后24h,雄虫和雌虫头部高度肿大,并伴有严重的口吸盘损害。给药后3d,虫体普遍出现局部肿大,雌、雄虫的受损皮层融合形成大的块状物,突出于体表,并见局灶性或广泛的皮层剥落,或因肿大的感觉结构破溃形成洞样外观。给药后7d,甲氟喹引起的虫体局部肿大和皮层损害与给药后3d相仿,并见局灶性皮层剥落、肿大,感觉结构的破溃和雌、雄虫口吸盘毁形。给药后14d,个别存活雄虫的虫体仍有轻度局部肿大,但其头部皮层褶嵴正常。结论甲氟喹可引起血吸虫成虫虫体局部肿大和广泛严重的皮层损害。     

蒿甲醚诱导日本血吸虫雌虫总抗氧化能力下降(英)

目的 观察蒿甲醚对日本血吸虫成虫总抗氧化能力的影响。 方法 体外将血吸虫在含蒿甲醚和氯化血红素的培养液内培养24 h后,或体内感染小鼠经蒿甲醚300mg/kg治疗6～24 h后,测定虫体的总抗氧化能力。 结果体外50μmol/L的蒿甲醚与氯化血红素伍用引起雌虫总抗氧化能力明显下降。体内蒿甲醚作用血吸虫6 h,即见雌虫的总抗氧化能力明显下降。体内、体外试验中,蒿甲醚对雄虫的总抗氧化能力均无影响。 结论 蒿甲醚诱导雌虫总抗氧化能力下降。     

蒿甲醚诱导日本血吸虫雌虫总抗氧化能力下降(英)

目的 观察蒿甲醚对日本血吸虫成虫总抗氧化能力的影响。 方法 体外将血吸虫在含蒿甲醚和氯化血红素的培养液内培养24 h后,或体内感染小鼠经蒿甲醚300mg/kg治疗6～24 h后,测定虫体的总抗氧化能力。 结果体外50μmol/L的蒿甲醚与氯化血红素伍用引起雌虫总抗氧化能力明显下降。体内蒿甲醚作用血吸虫6 h,即见雌虫的总抗氧化能力明显下降。体内、体外试验中,蒿甲醚对雄虫的总抗氧化能力均无影响。 结论 蒿甲醚诱导雌虫总抗氧化能力下降。     

环孢素A体外抗曼氏血吸虫合胞体超微结构的变化

[目的 ]探讨环孢素A体外抗曼氏血吸虫超微病理改变。 [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集虫体。将虫体放入含有 2 0 μg/ml环孢素A的M199培养液中体外培养。用扫描电镜和透射电镜观察药物所致的虫体损害。 [结果 ]药物作用后 ,大多数雄虫皮层肿胀、表面出现大小不一的结节、皮层外膜破溃、皮棘脱落、合胞体极度破坏 ;个别雄虫皮层出现空泡 ;雌虫皮层极度空泡变及合胞体受损。 [结论 ]环孢素A具有直接抗曼氏血吸虫的作用 ,合胞体受损是药物作用的主要机制。     

3种青蒿素衍生物对日本血吸虫吡喹酮抗性株童虫的体内作用效果观察

目的观察3种青蒿素衍生物双氢青蒿素、青蒿琥酯和蒿甲醚对日本血吸虫吡喹酮抗性株童虫的体内作用效果。方法以经11轮亚治疗剂量吡喹酮筛选的日本血吸虫为吡喹酮抗性株,以未暴露于吡喹酮的日本血吸虫作为吡喹酮敏感株,收集2虫株尾蚴感染小鼠,以300mg/kg双氢青蒿素、青蒿琥酯和蒿甲醚对感染后7~8 d童虫分别进行2次灌服用药(总剂量600 mg/kg),所有小鼠于感染后45 d解剖,收集小鼠体内成虫并计数,计算减虫率和减雌率。结果 300 mg/kg双氢青蒿素、蒿甲醚和青蒿琥酯2日疗法(总剂量600 mg/kg)对日本血吸虫吡喹酮敏感株7~8 d童虫的减虫率为69.8%~71.0%,减雌率为75.4%~79.8%;对日本血吸虫吡喹酮抗性株7~8 d童虫的减虫率为64.6%~66.1%,减雌率为69.3%~71.1%,差异均无统计学意义(均p0.05)。结论 日本血吸虫吡喹酮抗性株对青蒿素类衍生物双氢青蒿素、青蒿琥酯和蒿甲醚依然敏感,青蒿素衍生物与吡喹酮在日本血吸虫中不存在交叉抗药性。     

双氢青蒿素、青蒿琥酯和蒿甲醚连续给药及伍用治疗小鼠血吸虫病效果观察

目的观察双氢青蒿素、青蒿琥酯和蒿甲醚连续给药或伍用治疗小鼠血吸虫病的效果,为日本血吸虫病病原学治疗提供药物配伍实验依据。方法采用腹部贴片感染法,每鼠感染日本血吸虫尾蚴40±1条,分别于感染后6~8 d(童虫期)和34~36 d(成虫期),以300 mg/kg双氢青蒿素、青蒿琥酯和蒿甲醚连续给药及3种药物等剂量配伍给药,在感染后50 d解剖小鼠,收集成虫,计算减虫率和减雌率。结果在感染后6~8 d,双氢青蒿素、青蒿琥酯、蒿甲醚连续3 d单独给药和3种药物等剂量配伍给药,小鼠减虫率为79.5%~86.0%;减雌率为79.4%~86.7%,差异均无统计学意义(P均>0.05);在感染后34~36 d给药,减虫率为73.8%~75.8%,减雌率为88.7%~93.1%,差异无统计学意义(P均>0.05)。结论双氢青蒿素、青蒿琥酯和蒿甲醚连续给药及伍用治疗小鼠血吸虫病效果无显著差异。     

Transmission electron microscopic observations on ultrastructural damage in juvenile Schistosoma mansoni caused by artemether.

Artemether, a derivative of the antimalarial artemisinin, has been shown to induce rapid and extensive alteration to the tegument of juvenile Schistosoma japonicum, S. mansoni and S. haematobium. Less is known with regard to ultrastructural damage caused by artemether; therefore, the present work was designed to assess the damage in juvenile S. mansoni. Mice infected with S. mansoni were treated intragastrically with a single dose of 400 mg/kg artemether 21 days post-infection. Between 8 h and 14 days after treatment groups of two mice were sacrificed, and schistosomula recovered for transmission electron microscopic observations. Ultrastructural damage was seen in the tegument, subtegumental musculature, parenchymal tissues and gastrodermis. It was already apparent 8 h after drug administration and increased gradually to reach a peak, 7 days post-treatment. Tegumental alterations were characterised by swelling, vesiculation and degeneration of sensory structures. Damage in subtegumental musculature, parenchymal tissues and gastrodermis included swelling, focal or extensive lysis, and decrease in granular endoplasmatic reticulum. Fourteen days after treatment ultrastructural damage was still seen in most schistosomula, however, there was partial repair in some specimens. The ability of artemether to cause extensive ultrastructural damage to juvenile S. mansoni correlates with its schistosomicidal effects and confirms earlier findings with S. japonicum.     

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.     

吡喹酮、阿苯达唑和甲苯达唑对小鼠细粒棘球蚴生发膜超微结构的影响

小鼠感染的细粒棘球蚴囊经吡喹酮、阿苯达唑和甲苯达唑治疗后,其生发膜的超微结构均示有广泛的变化,主要是皮层基质变性、溶解和空泡变化;皮层细胞核周胞质的溶解、空泡形成,线粒体密集、变性、肿大,间质及肌束的广泛或局灶性溶解,以及囊腔面的溶解和脱落。甲苯达唑和阿苯达唑尚可引起角质层的损害及核染色质减少等。     

Ultrastructural alterations in adult Schistosoma mansoni, harbored in non-antihelminthic treated and low-inflammatory mice by transmission electron microscopy (TEM)

This original study suggests that alterations observed on tegumental structure and egg quality of adult Schistosoma mansoni harvested from TS mice are due to their high immune tolerogenic and low-inflammatory capacity. The tegument of worms harvested from genetically selected mice for extreme phenotypes of immune oral tolerance, resistance (TR) and susceptibility (TS) were analyzed by transmission electron microscopy (TEM). Parasites recovered from TR mice showed no tegumental morphological changes. However, specimens collected from TS mice exhibited tubercle swelling with blunted and shortened spines in lower density. These tegumental alterations were similar to those described with artemether or praziquantel treatment, but without to affecting the worm surveillance, supporting observations that the host immune system influences the development and function of the tegument of worms harbored in non-antihelminthic treated TS mice. TS mice showed a higher percentage of dead eggs and a lower percentage of immature eggs than TR mice, but had similar quantities of collected eggs. This suggests that in TS mice the alterations in adult worm tegument prevented egg development, but not egg production or worm survival. These results corroborate our previous scanning electron microscopy (SEM) study indicating the influence of the host immune regulatory profile on the development and function of the worm's reproductive system and tegument.     

Morphological tegument alterations of adult Schistosoma mansoni, harbored in non anti-helminthic treated, high-immune-tolerogenic and low-inflammatory mice

The present study exhibits original results of S. mansoni tegumental alterations due to contact with the immune system of non anti-helminthic treated mice. We compared, by SEM, the tegument of adult worms recovered from strains of mice genetically selected to extreme phenotypes of resistance (TR strain) and susceptibility (TS strain) to egg-albumin oral tolerance (OT). The parasites recovered from TR mice displayed no morphologic alteration, while specimens collected from TS mice presented tubercle swelling with blunted and shortened spines in lower density, increased sensory organelle numbers, fusion and tegumental ridge peeling. These tegument alterations were similar to those described for Artemether or Praziquantel treatment, supporting observations that the host immune system influences the development and function of the tegument of worms harbored in both anti-helminthic treated and non-treated mice. Our results are indicative that the development and function of the worm tegument depend on the immune regulatory capacity of each individual host.     

Histopathological changes in juvenile Schistosoma haematobium harboured in hamsters treated with artemether

Histopathological changes in juvenile Schistosoma haematobium, caused by artemether administered to the infected hamsters, were studied. Hamsters were infected with S. haematobium cercariae, and after 28 days, a single dose of artemether (300 mg/kg) was administered intragastrically. After 24 h, 72 h and 7 days, groups of two hamsters were sacrificed, and livers were removed, fixed and processed routinely, and examined by light microscopy. After 24 h, 93% of the schistosomulae examined showed degeneration, which included swelling of the tegument, adherence of inflammatory cells to the damaged tegument, collapsed and damaged intestine, and infiltration of inflammatory cells, predominantly lymphocytes. After 72 h, the intensity of damage increased, including severe swelling of the tegument, loss of definition in the internal structures, collapse of intestine accompanied by release of pigment particles to the parenchymal tissues, and emergence of dead schistosomulae. Seven days after treatment, the number of dead schistosomulae increased, and most of them developed to an early- or late stage of dead worm granuloma. Meanwhile, 12% of the schistosomulae showed a normal appearance, which suggested that those schistosomulae that had survived the treatment were recovered to normal. The results demonstrated that artemether effectively acts against the juvenile stages of S. haematobium and confirms earlier results with S. japonicum and S. mansoni.     

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。