灭螺药氯硝柳胺急性暴露对斑马鱼胚胎/幼鱼代谢能力的影响

氯硝柳胺（Niclosamide, NIC）是我国目前使用最久，也是使用量最多的化学灭螺药物，其带来的环境问题和生物安全问题逐渐引起人们重视。我们前期研究证实，NIC急性暴露会干扰斑马鱼幼鱼脂代谢途径，该研究在此基础上，进一步深入研究环境相关浓度NIC急性暴露对胚胎/幼鱼代谢水平的干扰效应。将受精2 h内的健康斑马鱼胚胎暴露于环境相关浓度的NIC（浓度依次为0，5，10，20和40 μg/L）至120 h。结果表明，和对照组相比，40 μg/L NIC暴露会显著改变幼鱼体内代谢产物，如葡萄糖和乳酸含量（P < 0.05 和P < 0.05）；另外，NIC暴露还会显著抑制幼鱼体内柠檬酸合成酶（CS）活力，而乳酸脱氢酶（LDH）活力被显著增强（P < 0.05 和P < 0.05）。代谢相关过氧化物酶体增值剂激活受体（PPAR）家族中的两个基因，pparα和pparγ，在NIC暴露组中其mRNA的相对表达水平都被显著上调（P < 0.05 和P < 0.05）。上述结果说明，环境相关浓度的NIC急性暴露会对早期胚胎的发育及幼鱼体内代谢水平造成干扰，表现为改变体内代谢相关基因的表达水平，并对代谢相关酶的活力和代谢产物的含量造成影响。

Effects of Acute Exposure to Niclosamide on Metabolism in Zebrafish embryos/larvae

Niclosamide (NIC) is one of the commercially molluscicide. With long-term and large-scale using of NIC in China has resulted in ubiquitous environmental and biological safety problems, gradually attracted human attention. Our previous study revealed that acute exposure to NIC disrupted lipid metabolism in zebrafish larvae. Base on that, in our present study, we intended to further study the disruptive effect of NIC on the mechanism in zebrafish embryos/larvae. Healthy zebrafish embryos within 2 h post-fertilization (hpf) were acutely exposed to environmentally realistic concentration of NIC (0, 5, 10, 20 and 40 μg/L, respectively) until 120 hpf. Our results showed that 40 μg/L NIC exposure significantly altered the content of metabolites, such as glucose and lactate, compared with the control. (P < 0.05 and P < 0.05, respectively); additionally, exposure to NIC also significantly inhibited citrate synthase (CS) activity, while a significant increase of lactate dehydrogenase (LDH) activity was observed in 40 μg/L NIC treated group (P < 0.05 and P < 0.05, respectively). Two relative genes, pparα and pparγ, mRNA expressions were significantly increased in 40 μg/L NIC treated group (P < 0.05 and P < 0.05, respectively). Our results indicate that acute exposure to NIC at an environmentally realistic concentration disturbs the metabolism in zebrafish embryos/larvae, as well as alters the expression of genes related to metabolism, changes the activity of enzymes and the contents of metabolites.