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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。
Objective: To study the effects of nitidine chloride and hydroxycamptothecin on the development of zebrafish. Methods: The nitidine chloride (NC) was divided into five dosage groups (5.00, 3.15, 2.00, 1.58, 1.12 mg.L-1). The final concentration of DMSO in each group was 0.01%, and 0.01% DMSO was used. Incubation solution group and control group (pure hatch fluid group). Hydroxycamptothecin (HCPT) was divided into 5 groups containing doses of 16.00, 10.00, 6.50, 4.00, and 2.50 mg.L-1. The final concentration of DMSO in each group was 0.01%. A control group (pure hatching fluid group) and a hatching fluid group containing 0.01% DMSO were also set. Normally developed zebrafish embryos 6 h (6 hpf) and 48 h (48 hpf) were microscopy and randomly assigned to the above groups, 20 embryos per experimental group. Observe the death and malformation of the embryos at 72 hpf. RESULTS: In the 6 hpf experimental group of nitidine chloride, the LC50 was 1.66 mg.L-1, and the EC50 was 1.33 mg.L-1; in the 48 hpf experimental group, The LC50 was 2.51 mg.L-1 and the EC50 was 2.02 mg.L-1. In the 6 hpf experimental group of HCPT, the LC50 was 4.21 mg.L-1 and the EC50 was 3.29 mg.L-1. In the 48 hpf group, the LC50 was 7.70 mg.L-1 and the EC50 was 6.18 mg.L. -1. The mortality and malformation rate of zebrafish embryos decreased significantly with the decrease of concentration of nitidine chloride and hydroxycamptothecin and the delay of administration time (P<0.01). CONCLUSION: The sensitivity of 6 hpf embryos to nitidine chloride and hydroxycamptothecin is greater than 48 hpf. The developmental toxicity of nitidine chloride to zebrafish embryos is greater than that of hydroxycamptothecin.