吉非替尼对斑马鱼胚胎发育及肿瘤耐药基因表达的影响

发布时间：2018-03-19 10:54

  本文选题：斑马鱼　切入点：吉非替尼　出处：《重庆医学》2017年32期 　论文类型：期刊论文

【摘要】：目的研究吉非替尼对斑马鱼早期胚胎发育及abcb4肿瘤耐药基因表达的影响。方法实验动物采用斑马鱼,实验分为吉非替尼组、阿霉素和吉非替尼的混合液组、空白对照组。将吉非替尼稀释成不同浓度梯度的药液,分别处理受精后0.5~1.5h(0.5~1.5hpf)的斑马鱼胚胎,观察胚胎和幼鱼的死亡率、孵化率及畸形率变化。统计各浓度不同时间点的胚胎死亡率,计算出IC_(50)的数值;统计48hpf和72hpf的胚胎孵化率及120hpf的畸形率;收集不同组别的斑马鱼胚胎,通过实时荧光定量PCR,检测斑马鱼胚胎中abcb4基因的表达量。结果计算出吉非替尼在斑马鱼胚胎中的IC_(50)为16.18μmol/L。与对照组比较,高剂量吉非替尼(≥20μmol/L)显著抑制胚胎的孵化,并有明显的胚胎致死效应和致畸效应;吉非替尼组的斑马鱼胚胎abcb4基因的mRNA水平变化不显著,而阿霉素和吉非替尼的混合液组的abcb4基因的mRNA水平有明显变化(P0.05)。结论吉非替尼对斑马鱼早期胚胎中abcb4肿瘤耐药基因的表达水平无明显影响(P0.05),但是吉非替尼能逆转易耐药药物阿霉素的耐药作用,提示使用斑马鱼可以构建肿瘤耐药模型。
[Abstract]:Objective to study the effects of gefitinib on the development of early embryos and the expression of drug-resistant genes in abcb4 tumor of zebrafish. Methods zebrafish were divided into three groups: gifitinib group, doxorubicin and gefitinib mixture group. In the blank control group, the zebrafish embryos were treated with different concentration gradient solution of gefitinib, and the death rates of embryos and young fish were observed, and the embryos of zebrafish were treated with 0.5 ~ (1.5) h ~ (-1) and 0.5 ~ (5) h ~ (PF) after fertilization, respectively. Change of hatching rate and deformity rate. Count the embryo mortality rate at different time points of different concentration, calculate the value of ICSP 50), calculate the embryo hatchability rate of 48hpf and 72hpf and the deformity rate of 120hpf; collect different groups of zebrafish embryos, The expression of abcb4 gene in zebrafish embryos was detected by real-time fluorescence quantitative PCR. The ICSP 50 of gifitinib in zebrafish embryos was calculated to be 16.18 渭 mol / L. Compared with the control group, high dose of gifitinib (鈮，

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