首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到17条相似文献,搜索用时 218 毫秒
1.
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。  相似文献   

2.
青蒿琥酯抗日本血吸虫童虫和成虫作用的研究   总被引:2,自引:0,他引:2  
目的 观察青蒿琥酯对不同阶段日本血吸虫的损害作用,揭示青蒿琥酯的杀虫机制.方法小鼠感染尾蚴18 d时给予青蒿琥酯300 mg/kg,24 h后灌注法收集童虫,并用紫外吸收法和Bradford标准曲线法测定青蒿琥酯对日本血吸虫18 d童虫DNA和蛋白质含量的影响;分别将10条虫体在含有3H胸腺嘧啶核苷的培养基中培养24 h后,用滤膜法和匀浆法测定青蒿琥酯对标记核苷掺入童虫DNA的影响;感染血吸虫尾蚴21 d的小鼠一次性灌服青蒿琥酯300 mg/kg,给药后21 d,灌注法收集成虫,观察青蒿琥酯对日本血吸虫成虫生殖器官大小及生殖细胞发育的影响;小鼠感染血吸虫33 d时给予同样的青蒿琥酯进行治疗,24 h和48 h后处死小鼠,将肝脏制作组织切片,在光镜下观察同等剂量青蒿琥酯引起的成虫肝移和形态学变化的影响.结果 青蒿琥酯体内作用18 d的虫体,24 h后,童虫的DNA和蛋白质含量均较对照组明显减少,减少率分别为23.0%和33.6%(P<0.01);在含有3H胸腺嘧啶核苷的培养基中培养24 h后,童虫摄入标记的核苷及核苷掺入童虫DNA的量较对照组也明显减少,减少率分别为61.1%和40.8%(P<0.01);21 d给药组小鼠体内雌虫卵巢的成熟、发育受到了抑制;药物作用于虫体33 d后能明显引起虫体形态的变化,特别是虫体体表.结论 青蒿琥酯能减少日本血吸虫童虫蛋白质和DNA的含量,能明显抑制虫体对标记核苷的摄入以及标记核苷掺入虫体DNA的量,能引起虫体体表明显的组织形态学变化,并且能抑制雌虫卵巢的发育,降低或抑制雌虫的产卵,能有效减轻血吸虫病的病情和控制传播.  相似文献   

3.
目的了解蒿甲醚和青蒿琥酯对小鼠曼氏血吸虫作用的效果.方法将小鼠随机分成12个实验组及1个对照组,以皮下注射的方法,每鼠接种约80条尾蚴,接种尾蚴46 d后,分别以蒿甲醚或青蒿琥酯灌胃治疗,第1天,分别以400、300、200 mg/kg的剂量1次灌胃;第2~7天,则每天分别按以上剂量的半量灌胃,7 d灌胃的总剂量分别为1 600、1 200、800 mg/kg.总量1剂组,在第7天,分别按1 600、1 200、800 mg/kg剂量1次灌胃.另设感染阳性对照组,不加治疗. 结果蒿甲醚7日疗法1 600、1 200、800 mg/kg剂量组减虫率分别为53.0%、49.0%和53.0%,减雌率为78.0%~82.0%,总量1剂组效果与7日疗法基本相同.青蒿琥酯7日疗法相应剂量减虫率分别为16.0%、37.0%和49.0%.结论蒿甲醚和青蒿琥酯对小鼠曼氏血吸虫具有一定的杀虫效果,蒿甲醚在疗效和毒性方面稍佳.  相似文献   

4.
青蒿琥酯预防曼氏血吸虫病的实验研究   总被引:8,自引:0,他引:8       下载免费PDF全文
目的 研究青蒿琥酯对小鼠曼氏血吸虫病的预防作用及优化给药方案。 方法 小鼠尾部接触感染曼氏血吸虫尾蚴后口服青蒿琥酯 ,灌注法收集计数虫体数和雌虫数 ,镜检计数肝脏和肠的虫卵 ,统计减虫率、减雌率和平均产卵量 ,分析青蒿琥酯不同给药时间、剂量、疗程的预防效果。 结果 青蒿琥酯预防小鼠曼氏血吸虫病的最佳剂量为 3 0 0mg/kg ,14、2 1d童虫对药物最为敏感 ,减虫率分别为 84%和 93 %。小鼠感染 14d后每周口服 1次青蒿琥酯3 0 0mg/kg ,连续 4wk ,减虫率达 99% ;感染 14或 2 1d后每 2wk口服 1次青蒿琥酯 3 0 0mg/kg ,连续 4wk ,减虫率达 97%或 96%。各服药组平均产卵量与对照组差异具有显著性意义 结论 青蒿琥酯可杀灭曼氏血吸虫童虫 ,影响雌虫发育产卵 ,有效预防曼氏血吸虫病。建议应用青蒿琥酯预防曼氏血吸虫病的给药方案为感染 14或 2 1d后首服 ,每 1或 2周服用 1次。  相似文献   

5.
蒿甲醚诱导日本血吸虫雌虫总抗氧化能力下降(英)   总被引:3,自引:1,他引:3       下载免费PDF全文
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。  相似文献   

6.
蒿甲醚诱导日本血吸虫雌虫总抗氧化能力下降(英)   总被引:3,自引:0,他引:3       下载免费PDF全文
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。  相似文献   

7.
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。  相似文献   

8.
本文叙述了用曼氏血吸虫成虫分离的表皮制剂免疫小鼠获得单克隆抗体的方法。这种抗体能杀死童虫并可识别童虫的表面抗原。实验采用曼氏血吸虫波多黎各株和光滑双脐螺。成虫从感染6周的仓鼠门静脉中检获,尾蚴用Ramalho-Pinto法发育为童虫,肺部童虫可从感染1000条尾蚴的CBA/Ca  相似文献   

9.
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。  相似文献   

10.
本文用扫描电镜观察了不同剂量吡喹酮对小鼠体内两性曼氏血吸虫成虫体表的影响。实验用Tuck株的雌雄小鼠,在感染复性波多黎各株曼氏血吸虫尾蚴后70天,分别皮下注射混悬于Cremophor EL中2%的吡喹酮10、25、50、100、200及500mg/kg。在治后1及4小时取虫,按扫描电镜常规制作成标本。在扫描电镜下观察虫体体表的变化,另用未经药物治疗的正常成虫作对照。结果如下: 雄虫:用吡喹酮10mg/kg时,在给药后1小时,仅在某些雄虫背部体表及体棘结节  相似文献   

11.
Praziquantel and artemether are safe and efficacious antischistosomal drugs that act against different developmental stages of the parasite: praziquantel against adult worms and artemether against schistosomula. A combined treatment has been suggested as a strategy for transmission control. Recent laboratory experiments with rabbits with a mixed infection of Schistosoma japonicum parasites of different ages confirmed the effectiveness of a combination therapy. In the present work, we assessed the effect of a combined treatment on adult worms of S. japonicum and found significantly higher worm reduction rates than with a single dose of praziquantel. In a next step, we extended the study of the combined treatment to Schistosoma mansoni. A combined treatment with 75 mg/kg praziquantel and 150 mg/kg artemether was administered to hamsters infected with juvenile and adult S. mansoni. The two drugs, administered simultaneously or spaced by 6 h, 1, 3 or 7 days, resulted in significantly higher worm reduction rates than a single treatment with praziquantel. A combination therapy with increased doses of 100 mg/kg praziquantel and 300 mg/kg artemether showed very high worm reduction rates of 90% and above, however, some hamsters died in five different combined treatment experiments, suggesting that these drug concentrations were too high. We conclude that a combined treatment with praziquantel and artemether at the lower doses is safe and more effective than praziquantel alone, which forms a foundation for designing respective clinical trials in humans.  相似文献   

12.
目的 观察三苯双脒、青蒿琥酯、蒿甲醚、或吡喹酮单剂、多剂给药,及其伍用治疗感染华支睾吸虫大鼠的疗效。 方法 147只SD大鼠各感染50个华支睾吸虫囊蚴,于感染后42~44 d分组治疗。各药物采用灌胃给药。①60只感染大鼠随机分为11组(每组4~5只),分别为三苯双脒150 mg/kg(顿服)、75 mg/(kg·d)×2 d、50 mg/(kg·d)×3 d和25 mg/kg(tid)×2 d组;吡喹酮150 mg/kg(顿服)、75 mg/(kg·d)×2 d和25 mg/kg(tid)×2 d;青蒿琥酯或蒿甲醚75 mg/kg(顿服)和37.5 mg/(kg·d)×2 d组。②另87只感染大鼠随机分为15组(每组4~6只),用青蒿琥酯或蒿甲醚(30 mg/kg)分别与吡喹酮(150 mg/kg)、三苯双脒(50 mg/kg和75 mg/kg)伍用组;三苯双脒(50 mg/kg)与吡喹酮(150 mg/kg)伍用组;三苯双脒(75 mg/kg)与吡喹酮(187.5 mg/kg)伍用组,及各药的单用组。并设同批感染未治疗对照组。受治鼠于治疗后2周剖杀,收集胆管和肝组织内的残留华支睾吸虫,计算各组的平均虫数和减虫率,用非参数统计方法(Mann-Whitney秩和检验)对相应组间的平均虫数进行分析。 结果 感染华支睾吸虫的大鼠口服单剂三苯双脒或吡喹酮(150 mg/kg)的减虫率分别为57.2%和63.8%。三苯双脒各小剂量多次给药组的减虫率稍高,达77.1%~79.4%,而吡喹酮小剂量多次给药组的减虫率则为50.6%~54.2%。但两种药物各组间的平均虫数的差异无统计学意义。青蒿琥酯和蒿甲醚各单剂给药组与小剂量多次给药组的减虫率均较高,分别为90.4%~98.5%和100%。三苯双脒小剂量(50或75 mg/kg)与吡喹酮(150 mg/kg 或187.5 mg/kg)伍用治疗,减虫率为74.9%~100%,高于其各单药组的减虫率(26.9%~79.6%)。青蒿琥酯或蒿甲醚小剂量(30 mg/kg)与吡喹酮(150 mg/kg)或三苯双脒(50或75 mg/kg)伍用治疗,减虫率为74.9%~97.9%,亦高于其各药组的减虫率(24.8%~79.6%)。 结论 青蒿琥酯、蒿甲醚、吡喹酮和三苯双脒均为有效的抗华支睾吸虫药物,各药物小剂量伍用具有增效作用。  相似文献   

13.
目的实验研究在吡喹酮药物压力下中国大陆日本血吸虫对吡喹酮产生抗药性的可能性。方法取采自湖南省血吸虫病流行区湖滩现场和江苏省实验室传代的感染性钉螺实验室逸蚴,获得日本血吸虫尾蚴感染小鼠,从感染鼠肝脏分离成熟虫卵孵化毛蚴感染湖北钉螺,建立现场采集株和实验室传代株日本血吸虫小鼠钉螺实验室生活史循环。用定量尾蚴(40条/鼠)感染小鼠,感染35d后将小鼠随机分为对照组和抗性诱导组:对照组小鼠感染后45d解剖收集肠系膜静脉和肝门脉静活虫体,计算虫负荷(条/鼠);抗性诱导组小鼠采用灌胃法一次口服亚治疗剂量吡喹酮进行治疗,服药22d后解剖收集肠系膜静脉和肝门脉静存活虫体。计算虫负荷(条/鼠)和减虫率,完成首轮诱导。取抗性诱导组小鼠肝脏,分离虫卵,实验室孵化出毛蚴重新感染钉螺,感染后的钉螺经25℃生化培养箱内饲养60~70d后,分离感染性钉螺并逸蚴,用成熟尾蚴感染小鼠,开始新一轮循环诱导。首轮诱导吡喹酮口服剂量为100mg/kg,后每循环2~3轮增加100mg/kg口服剂量。取完成8轮诱导后和未经诱导原代虫株的尾蚴感染小鼠,感染35d后分别采用300mg/kg和600mg/kg吡喹酮一次性灌胃治疗感染小鼠,服药后14d解剖感染鼠,收集活虫,计算各虫株减虫率,评价虫株经8轮诱导后对吡喹酮敏感性的变化。结果在实验室内建立了江苏实验室传代株和湖南现场采集株2个虫株,并对其实施了8轮诱导。江苏实验室传代株在小鼠体内经第1轮口服100mg/kg吡喹酮治疗后减虫率为22.3%,第8轮口服300mg/kg吡喹酮治疗后减虫率为53.7%,减虫率随口服吡喹酮剂量增加而增加;湖南现场采集株在小鼠体内经第1轮口服100mg/kg吡喹酮治疗后减虫率为66.8%,第8轮口服300mg/kg吡喹酮治疗后减虫率仅为20.6%,减虫率随口服吡喹酮剂量增加而显著降低。未经吡喹酮诱导的江苏实验室传代株在小鼠体内经300mg/kg和600mg/kg吡喹酮治疗后,减虫率分别为71.5%和97.4%;经8轮吡喹酮筛选治疗后该虫株减虫率降至32.6%和68.1%。未经吡喹酮诱导的湖南现场采集株在小鼠体内经300mg/kg和600mg/kg吡喹酮治疗后,减虫率分别为70.8%和97.5%;经8轮吡喹酮筛选治疗后该虫株减虫率降至45.7%和61.9%。结论中国大陆日本血吸虫在吡喹酮持续药物压力下可产生抗药性,但不同虫株间对吡喹酮敏感性存在差异,药物压力下产生抗性的潜能也存在差异。中国大陆日本血吸虫吡喹酮抗性株的建立,可为研究日本血吸虫吡喹酮抗性机制及其检测和监测技术奠定基础。  相似文献   

14.
Some have claimed that triclabendazole, a safe and efficacious drug for the treatment of fascioliasis, also exhibits antischistosomal properties, but results are conflicting. We assessed the effect of triclabendazole and its two main metabolites against two different strains of Schistosoma mansoni harbored in mice. Low worm burden reductions (18.6-35.9%) were observed in mice infected with an Egyptian strain of S. mansoni and treated with a single dose of 120 mg/kg 3 days before infection or single/double doses of 120-200 mg/kg 7 weeks after infection. Triclabendazole failed to significantly reduce hepatic and intestinal tissue egg loads, and eggs of all developmental stages were observed. Administration of 400 mg/kg of either triclabendazole, triclabendazole sulphone, or triclabendazole sulfphoxide to mice infected with a Liberian strain of S. mansoni resulted in worm burden reductions < 10%. In comparison, high worm burden reductions (82-100%) were observed in S. mansoni-infected mice treated with single oral doses of 400, 500, or 500 mg/kg twice a day praziquantel, regardless of the S. mansoni strain. We conclude that triclabendazole and its main metabolites display weak and inconsistent schistosomicidal activities.  相似文献   

15.
We comparatively assessed the in vivo efficacy of artemether, artesunate, praziquantel and tribendimidine against different stages of Clonorchis sinensis. Rats were infected with 40-50 C. sinensis metacercariae, and drugs were administered singly by the oral route at different dosages. Rats were dissected 2-4 weeks post-treatment and C. sinensis trematodes were removed from the liver and bile ducts and counted. We used a negative binomial regression model to test the effect of drug and dosage in terms of worm burden reduction. Single 150 mg/kg oral doses of artesunate, artemether, tribendimidine and praziquantel, administered to rats infected with adult C. sinensis, resulted in mean worm burden reductions of 100, 100, 89.5 and 80.7%, respectively (all P<0.001). Halving the dose to 75 mg/kg still resulted in highly significant worm burden reductions for artesunate, artemether and tribendimidine (71.4-100%), but not for praziquantel (20.7%). In the juvenile infection model, a single 150 mg/kg oral dose of tribendimidine and praziquantel resulted in mean worm burden reductions of 99.1 and 90.0%, respectively, whereas considerably lower reductions were observed for artemether (59.2%) and artesunate (57.6%) when used at the same single dose. The in vivo results presented here with the artemisinins and tribendimidine provide further data for clinical investigations to assess the safety and efficacy of these drugs in clonorchiasis patients.  相似文献   

16.
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.  相似文献   

17.
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.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号