中文摘要：

目的应用模式生物秀丽隐杆线虫研究中药芫花的主要成分之一芫花素的毒性作用及机制。方法分别以芫花素0.1,1,10和100μmol·L^-1处理野生型或转基因型秀丽隐杆线虫（简称线虫）24,48和72 h,显微镜下观察野生型线虫头部摆动次数、身体弯曲次数、存活天数、后代数目、平均排泄循环长度和咽泵行为,并观察转基因型线虫γ-氨基丁酸（GABA）能神经元荧光强度,计数神经元数目。结果 （1）野生型线虫：与正常对照组比较,芫花素处理24 h后,芫花素1～100μmol·L^-1组线虫头部摆动和身体弯曲次数显著减少（P〈0.05,P〈0.01）;48 h后,芫花素0.1μmol·L^-1组身体弯曲次数显著减少（P〈0.05）,1～100μmol·L^-1组头部摆动和身体弯曲次数显著减少（P〈0.01）,100μmol·L^-1组平均排泄循环长度显著增加（P〈0.05）且咽泵行为显著减少（P〈0.01）;72 h后,芫花素0.1～100μmol·L^-1组头部摆动和身体弯曲次数均显著减少（P〈0.05,P〈0.01）,平均排泄循环长度显著增加（P〈0.05,P〈0.01）,咽泵行为显著减少（P〈0.05,P〈0.01）。（2）转基因型线虫：与正常对照组比较,芫花素处理24 h后,芫花素1～100μmol·L^-1组转基因型线虫GABA能神经元荧光强度显著降低（P〈0.05,P〈0.01）;48 h后,芫花素1～100μmol·L^-1组GABA能神经元荧光强度显著降低（P〈0.05,P〈0.01）且VD神经元数目显著减少（P〈0.01）;72 h后,芫花素0.1～100μmol·L^-1组GABA能神经元荧光强度显著降低（P〈0.05,P〈0.01）,1～100μmol·L^-1组AVL神经元数目显著减少（P〈0.05,P〈0.01）,10和100μmol·L^-1组VD神经元数目显著减少（P〈0.05,P〈0.01）。结论芫花素对秀丽隐杆线虫具有一定的毒性作用,主要表现为运动行为抑制,其毒性机制可能与GABA能神经元损伤有关。

英文摘要：

OBJECTIVE To explore the toxicity and mechanisms of genkwanin, one of the main components of Flos Genkwa, using the model organism Caenorhabditis elegans （C. elegans） assay system. METHODS Both wild-type and transgenic strains of C. elegans were treated with genkwanin 0.1, 1, 10 and 100 μmol·L^-1 for 24, 48 and 72 h, respectively. The head thrashes, body bends, lifespan, brood size, mean defecation cycle length and pumping behavior of the wild-type C. elegans as well as the fluo- rescence intensity and the number of GABAergic neurons of the transgenic C. elegans were observed under microscopes. RESULTS ① Wild-type C. elegans： Compared with the normal control group, after treatment with genkwanin for 24 h, the times of head thrashes and body bends of C.elegans showed significant decreases （P〈0.05, P〈0.01） in genkwanin 1-100 μmol·L^-1 groups. After treatment with genkwanin for 48 h, the times of body bends showed a significant decrease （P〈0.05） in genkwanin 0.1 μmol·L^-1 group, the times of head thrashes and body bends showed a significant decrease （P〈0.01） in genkwanin 1- 100 μmol·L^-1 groups, but a significant increase of mean defecation cycle length （P〈0.05） and a decrease of pumping behavior （P〈0.01） were observed in genkwanin 100 μmol·L^-1 groups. After treatment with genkwanin for 72 h, a decrease in the times of head thrashes and body bends （P〈0.05, P〈 0.01）, an increase of mean defecation cycle length （P〈0.05, P〈0.01）, and a decrease of pumping behavior （P〈0.05, P〈0.01） in C. elegans were observed in genkwanin 0.1-100 μmol·L^-1 groups. ② Transgenic C. elegans. Compared with the normal control, after treatment with genkwanin for 24 h, the fluorescence intensity of GABAergic neurons of the transgenic C. elegans showed significant decreases （P〈 0.05, P〈0.01） in genkwanin 1-100 μmol·L^-1 groups. After treatment with genkwanin for 48 h, the fluores- cence intensity of GABAergic neurons （P〈0.05, P〈0.01） and the number