阿司咪唑对斑马鱼心脏毒性的初步研究

Preliminary study of astemizole's cardiotoxicity to zebrafish

目的研究阿司咪唑对斑马鱼的心脏毒性,为斑马鱼的心脏毒性模型提供依据。方法选择1、4、10、20μmol·L-1的阿司咪唑观察其对72 hpf(hour post fertilization)斑马鱼的形态影响,包括畸形、心囊水肿、血细胞在心区堆积等情况,计算心率、死亡率及EC50,测量静脉窦-动脉球(SV-BA)间距,以及对2 hpf斑马鱼心脏发育的影响。结果阿司咪唑处理后,斑马鱼出现出心率下降、SV-BA间距增大、血细胞在心区堆积、全身无血流、心囊水肿、心脏停止跳动等中毒现象,并具有时间、剂量依赖性;同时观察到阿司咪唑对2 hpf斑马鱼的心脏发育有明显影响。结论利用阳性药物阿司咪唑探讨药物对斑马鱼心脏功能和发育方面的毒性,有助于建立基于斑马鱼的心脏毒性评价筛选体系。

Aim To study the cardiotoxicity of astem- izole to zebrafish embryos and to supply the reliable as- surance in establishing eardiotoxieity model of ze- brafish. Methods Zebrafish of 72 hrs post fertiliza- tion was treated with astemizole at various concentra- tions including 1, 4,10, 20 and 40 μmol · L-1. The effect of astemizole on heart morphology including heart deformity, pericardial edema, hemocyte accumulation was observed. Heart rate, death rate and the EC50 were calculated. The distance between sinus venosus and bulbus arteriosus （ SV-BA ） was measured. Zebrafish of 2 hrs post fertilization was treated with astemizole to observe its effect on heart development. Results De- creased heart rate, increased distance between sinusvenosus and bulbus arteriosus of zebrafish embryos, hemocytes accumulation in cardiac region, whole body without blood flow, pericardial edema and the heart stoping beating emerged in zebrafish incubated with astemizole, and the toxicity presented in time-and dose-dependent manner. Developmental toxicity on heart appeared in zebrafish embryos treated with astem- izole. Conclusion Astemizole as a positive drug can be used to study cardiotoxicity to zebrafish both in function and development, whcih is helpful to establish cardiotoxicity assessment model with zebrafish.