雷帕霉素靶蛋白抑制剂Deforlimus体外抗细粒棘球原头蚴作用的研究  

In vitro effects of the mammalian target of rapamycin inhibitor deforolimus on Echinococcus granulosus protoscoleces

作　　者：木扎拜尔.木合塔尔 郑海亚 李亚芬 吕国栋[2] 罗兰[1,2] MUHETAER Muzhabaier;ZHENG Hai-ya;LI Ya-fen;LV Guo-dong;LUO Lan(Xin jiang Medical University, Pharmacy College of Xinjiang Medical University, Urumqi 830011, China;The First Hospital Affiliated with Xinjiang Medical University;Women＇s and Children＇s Health Care Hospital of the Kashgar Region)

机构地区：[1]新疆医科大学药学院,新疆乌鲁木齐830011 [2]新疆医科大学第一附属医院 [3]喀什地区妇幼保健院

出　　处：《中国病原生物学杂志》2017年第12期1157-1160,1164,共5页Journal of Pathogen Biology

基　　金：国家自然科学基金项目(No.81360251)

摘　　要：目的探讨哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)抑制剂Deforlimus体外抗细粒棘球绦虫原头蚴作用。方法分别用100、50、25、12.5μmol/L、6.25和3.125μmol/L Deforlimus体外干预细粒棘球绦虫原头蚴4d,采用伊红染色法检测原头蚴活性,绘制存活率曲线;通过扫描电子显微镜和透射电子显微镜,观察不同浓度干预组原头蚴的表面和内部超微结构变化。实验设空白对照和溶剂对照。结果 100、50、25、12.5、6.25和3.125μmol/L Deforlimus干预4d原头蚴存活率分别为(3.53±0.98)%、(15.67±2.59)%、(19.14±1.96)%、(26.47±2.18)%、(33.78±1.75)%和(37.96±3.57)%,与空白对照组(95.10±0.68)%和溶剂对照组(94.41±0.84)%比较差异均有统计学意义(P<0.05),且原头蚴的存活率与Deforlimus浓度和干预时间成反比;扫描电镜观察100μmol/L Deforlimus干预组原头蚴吸盘变形,顶突结构缺损,微毛损伤甚至消失。结论 mTOR抑制剂Deforlimus具有体外抗细粒棘球绦虫原头蚴作用,是一种潜在的抗包虫病药物。Objectives To examine the In vitro protoscolicidal effect of the mammalian target of rapamycin（mTOR）inhibitor deforolimus on Echinococcus granulosus protoscoleces. Methods E.granulosus protoscoleces were treated with deforolimus at a concentration of 100μmol/L,50μmol/L,25μmol/L,12.5μmol/L,6.25μmol/L,or 3.125μmol/L for 4 days in vitro,and the activity of protoscoleces were detected with eosin staining.The ultrastructure of protoscoleces from each group was observed using scanning electron microscopy（SEM）and transmission electron microscopy（TEM）. Results Deforolimus inhibited the viability of protoscoleces,and the effect was dose-and time-dependent.The survival rate of protoscoleces in each deforolimus group was significantly lower than that in the untreated group and the solvent control group（P〈0.05）.On day 4,protoscoleces treated with deforolimus at a concentration of 100μmol/L had a survival rate of（3.53±0.98）%,protoscoleces treated with a concentration of 50μmol/L had a survival rate of（15.67±2.59）%,protoscoleces treated with a concentration of 25μmol/L had a survival rate of（19.14±1.96）%,protoscoleces treated with a concentration of 12.5μmol/L had a survival rate of（26.47±2.18）%,protoscoleces treated with a concentration of 6.25μmol/L had a survival rate of（33.78±1.75）%,protoscoleces treated with a concentration of 3.125μmol/L had a survival rate of（37.96±3.57）%.SEM results indicated that suckers were deformed,the surface of the rostellum was disrupted,and microtrichia were damaged or missing in protoscoleces treated deforolimus at a concentration of 100μmol/L. Conclusion The mTOR inhibitor deforolimus inhibited the viability of the protoscoleces in vitro and might be a potential drug to treat hydatidosis.

关 键 词：雷帕霉素靶蛋白(mTOR)抑制剂 Deforlimus 细粒棘球绦虫 原头蚴 

分 类 号：R383.3[医药卫生—医学寄生虫学]