【摘要】 铅是环境中常见的污染物,为探讨Wnt信号通路在铅暴露引起的胚胎发育毒性中的作用,将斑马鱼胚胎随机分为10组,每组100个,以铅(0、6、12、24、48μmol/L)和Wnt信号通路的激活剂HLY78(5μmol/L)单独及联合处理斑马鱼胚胎4-144 h,利用实时定量PCR技术进行分析.结果显示,铅单独暴露能够引起wnt3a表达量降低,而HLY78处理能够抑制wnt3a表达量的进行改变,修复Wnt信号通路.利用EthoVision XT软件获取并分析斑马鱼的自主运动、心率和运动行为等毒性试验的有效参数.与对照组相比,单独铅暴露组可致斑马鱼胚胎死亡率和畸形率增高,以及孵化率、心率和仔鱼平均活力降低(P<0.05);加入Wnt信号通路的激活剂HLY78,与单独暴露组相比,死亡率和畸形率显著降低,孵化率、心率和仔鱼平均活力显著升高(P <0.05).各组间胚胎的自主运动没有显著差异.本研究结果表明铅暴露可影响斑马鱼胚胎的发育,使用HLY78激活Wnt信号通路能够显著地缓解铅暴露诱导的这些影响,预示破坏Wnt信号通路可能与铅诱导的发育毒性相关.(图5参28)更多还原

【Abstract】 The goal of this study was to investigate the role of Wnt signaling in mediating the developmental toxicity induced by lead(Pb) exposure using zebrafish(Danio rerio) embryos. Zebrafish embryos were randomly divided into 10 groups. Pb(0,6, 12, 24, 48 μmol/L) were respectively exposure to zebrafish embryos for 4–144 h post fertilization, with or without HLY78,an activator of the Wnt signaling pathway(5 μmol/L). The expression of wnt3 a was detected using quantitative real-time PCR(qRT-PCR). Pb exposure significantly decreased the expression of wnt3 a, and supplementation with HLY78 was able to reduce this effect. Mortality, hatchability, and malformation were observed and recorded. Spontaneous movement, heart rate, and locomotive behavior in larval zebrafish were recorded and analyzed using the Vision XT software. Pb exposure significantly decreased hatchability, heart rate, and swimming activities(P < 0.05). Furthermore, mortality and malformation were significantly increased(P < 0.05). Compared to individual Pb exposure, supplementation with HLY78 significantly increased hatchability, heart rate, and swimming activities(P < 0.05), and the mortality and malformation of larvae were significantly decreased(P < 0.05). However, there was no significant difference in the spontaneous movement of embryos between groups.Overall, Pb exposure induced a significant increase in developmental toxicity and decreased the expression of wnt3 a. Activation of Wnt signaling alleviated Pb-exposure induced developmental toxicity. Results in this study allow us to further understand the molecular mechanisms of Pb-induced developmental toxicity, which potentially involves the inhibition of Wnt signaling.更多还原