四氯双酚A对斑马鱼幼鱼运动行为的影响及神经毒性机制研究
Effects of Tetrachlorobisphenol A (TCBPA) on Locomotion Behavior of Zebrafish Larvae and Its Neurotoxic Mechanism
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摘要: 四氯双酚A(tetrachlorobisphenol A, TCBPA)作为四溴双酚A的替代品被广泛使用导致其在环境中被高频检出，但是目前其对于鱼类的毒性效应及机制还研究较少。本研究以斑马鱼胚胎为研究对象，将其暴露于不同浓度的TCBPA(0、2、20和200 μg·L-1)中120 h。通过测定斑马鱼幼鱼死亡率、孵化率、畸形率以及光暗刺激下的运动行为评估TCBPA对斑马鱼幼鱼发育的影响；通过检测幼鱼吖啶橙(AO)染色情况、氧化产物丙二醛(malonic dialdehyde, MDA)含量、抗氧化酶超氧化物歧化酶(superoxide dismutase, SOD)活力、神经递质多巴胺(dopamine, DA)含量以及DA合成关键基因的转录等方面阐明TCBPA对斑马鱼幼鱼的潜在毒性机制。结果发现，TCBPA在最高剂量组可以增加幼鱼畸形率、降低幼鱼游泳速度，并且伴随着头部发生细胞凋亡、体内DA含量降低。基因表达结果表明细胞凋亡相关基因p53和bax表达量升高而多巴胺合成相关基因(bdnf, th, dat, drd1和drd2)表达量降低。本研究表明TCBPA可能通过诱导细胞凋亡、降低DA含量以及影响相关基因的表达从而影响斑马鱼幼鱼的运动行为，相关结果可以为识别TCBPA的生态风险提供直接依据。Abstract: Tetrachlorobisphenol A (TCBPA) is widely used as an alternative to tetrabromobisphenol A and has been highly detected in the environment. However, its toxic effects and mechanisms are less studied in fish. In this study, using zebrafish as a study model, embryos were exposed to TCBPA at different concentrations (0, 2, 20 and 200 μg·L-1) for 120 hours post fertilization (hpf) and the developmental endpoints and locomotion behavior of larvae were measured. To explore the potential mechanisms of TCBPA, the acridine orange (OA) staining, the contents of malonic dialdehyde (MDA), superoxide dismutase (SOD), dopamine (DA) and expression of genes related to the cell apoptosis and dopamine signaling pathway were analysed. The results showed that TCBPA significantly decreased the swimming speed at the maximum exposure concentration, accompanied by a decrease in zebrafish larvae dopamine content and significant cell apoptosis in brain. Furthermore, the expression of genes related to cell apoptosis (p53 and bax) and dopamine signaling pathway (bdnf, th, dat, drd1 and drd2) were significantly changed. Our results demonstrate TCBPA exposure can induce cell apoptosis and decrease the DA content, and subsequently affect the locomotion behavior of zebrafish larvae. Our study can provide direct scientific evidence for identifying TCBPA risk assessment.
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Key words:
- tetrachlorobisphenol A /
- zebrafish /
- locomotion behavior /
- dopamine /
- cell apoptosis
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