氯化两面针碱和羟基喜树碱对斑马鱼胚胎发育的影响

目的:研究氯化两面针碱和羟基喜树碱对斑马鱼发育的影响。方法:氯化两面针碱(NC)分成5.00,3.15,2.00,1.58,1.12 mg.L-1等5个含药剂量组,各组的DMSO终浓度为0.01%,并设含0.01%DMSO的孵化液组及对照组(纯孵化液组)。羟基喜树碱(HCPT)分为16.00,10.00,6.50,4.00,2.50 mg.L-1 5个含药剂量组,各组的DMSO终浓度为0.01%。并设对照组(纯孵化液组)及含0.01%DMSO的孵化液组。在显微镜下将正常发育6 h(6 hpf)和48 h(48 hpf)的斑马鱼胚胎,随机分入以上各组中,每个实验组20颗胚胎。观察药物处理至72 hpf时,胚胎的死亡和畸形情况。结果:氯化两面针碱的6 hpf实验组中,半数致死浓度(LC50)为1.66 mg.L-1,半数致畸效应浓度(EC50)为1.33 mg.L-1;48 hpf实验组中,LC50为2.51 mg.L-1,EC50为2.02 mg.L-1。羟基喜树碱的6 hpf实验组中,LC50为4.21 mg.L-1,EC50为3.29 mg.L-1;48 hpf实验组中,LC50为7.70 mg.L-1,EC50为6.18 mg.L-1。斑马鱼胚胎的死亡率和畸形率随着氯化两面针碱和羟基喜树碱药物浓度的降低和给药时间的推迟而显著降低(P<0.01)。结论:6 hpf胚胎对氯化两面针碱和羟基喜树碱的药物敏感性均大于48 hpf;氯化两面针碱对斑马鱼胚胎的发育毒性大于羟基喜树碱。

Effect of Nitidine Chloride and Hydroxycamptothecine on Development of Zebrafish Embryo

Objective: To study the effect of nitidine chloride(NC) and hydroxycamptothecine(HCPT) on the development of zebrafish embryo. Method: The 6 h and 48 h post-fertilization zebrafish embryos were randomly treated with NC (5.00,3.15,2.00,1.58,1.12 mg·L^-1) and HCPT ( 16.00,10.00,6.50,4.00,2.50 mg·L^-1). The death rate and malformation rate of zebrafish embryos were observed after 72 h. Result: 50% lethal concentration (LC₅₀)of was 1.66 mg·L^-1 and 50% malformation effect concentration (EC₅₀) was 1.33 mg·L^-1 in NC 6 hpf group. LC₅₀ was 2.51 mg·L^-1 and EC₅₀ was 2.02 mg·L^-1 in NC 48 hpf group. In HCPT 6 hpf group,LC₅₀ was 4.21 mg·L^-1,EC₅₀ was 3.29 mg·L^-1;LC₅₀ was 7.70 mg·L^-1,EC₅₀ was 6.18 mg·L^-1 in the HCPT 48 hpf group. Death rate and malformation rate were decreased when the drugs concentration reduced and test time were delayed. Conclusion: zebrafish embryos of 6 hpf are more sensitive to NC and HCPT than embryos of 48 hpf; both NC and HCPT can cause embryotoxicity to zebrafish; NC is more toxic to the development of zebrafish embryos than HCPT.