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目的:探讨姜黄素对斑马鱼胚胎和幼鱼的急性毒性,为确定姜黄素对斑马鱼疾病模型的安全剂量提供依据。方法:镜下选用受精后3 h(3 hpf)及受精后5天(5 dpf)的斑马鱼胚胎及幼鱼,分别暴露在不同浓度梯度的姜黄素溶液及空白对照(养殖水)和溶剂对照[0.1%二甲基亚砜(DMSO)]中,观察暴露24 h、48 h、72 h、96 h胚胎及幼鱼的死亡率、畸形率、畸形形态以及胚胎的孵化率,计算半数致死浓度(LC50)、半数致畸浓度(EC50)、致畸指数(TI)。结果:斑马鱼死亡率、孵化率及畸形率呈浓度相关性,4μmol·L~(-1)组胚胎和幼鱼无死亡,但胚胎出现畸形,幼鱼无畸形,1.86μmol·L~(-1)浓度组胚胎无畸形出现;畸形的种类主要是卵黄囊肿大、心包水肿、血液黏滞、尾部溶解、尾部及脊柱弯曲、鱼鳍缺失、眼未发育;胚胎及幼鱼96 h的LC50值、EC50值及TI值分别为17.70μmol·L~(-1)、17.40μmol·L~(-1)、1.02和7.80μmol·L~(-1)、7.37μmol·L~(-1)、1.06。结论:姜黄素对斑马鱼胚胎及幼鱼有一定的急性毒性及致畸作用,作用于胚胎和幼鱼的最大安全浓度分别为1.86、4μmol·L~(-1)。
Aims: To investigate the acute toxicity of curcumin on zebrafish embryos and juveniles, and to provide a basis for determining the safe dosage of curcumin in zebrafish disease model. Methods: The zebrafish embryos and juvenile fish that were exposed to 3 hpf (3 hpf) and 5 dpf (5 dpf) after fertilization were exposed to different concentrations of curcumin solution, blank control (culture water) and solvent control [0.1% dimethylsulfoxide (DMSO)], the mortality, malformation rate, malformation morphology and embryo hatching rate of embryos and juveniles exposed to 24 h, 48 h, 72 h, 96 h were observed, and the lethal concentration (LC50), half teratogenicity (EC50) and teratogenic index (TI). Results: The mortality, hatchability and deformity rate of zebrafish showed a concentration-dependent manner. There was no death in 4μmol·L -1 embryos and juveniles, but embryo malformations, juvenile deformities, and 1.86μmol·L ~ (-1) 1). The deformities of the embryos were mainly deformity of yolk cyst, pericardial edema, blood viscosity, dissolution of tail, caudal and spine curvature, absence of fins and undeveloped eyes. LC50 value of embryo and juvenile 96 h EC50 and TI values were 17.70μmol·L -1, 17.40μmol·L -1, 1.02 and 7.80μmol·L -1, 7.37μmol·L -1, 1.06. CONCLUSION: Curcumin has certain acute toxicity and teratogenic effects on zebrafish embryos and juveniles. The maximum safe concentrations of curcumin on embryos and juveniles are 1.86 and 4μmol·L -1, respectively.