基于斑马鱼模型研究重金属镉对耳石发育的毒性效应及机制

Cadmium is a heavy metal element which have attracted extensive environmentally toxicological research. The environmental chemical analysis reveals the universality and potential risks of cadmium exposure in electronic waste dismantling field, heavy metal mining area and so on, especially during the gestation of maternal generation and the early development stage of newborn. Cadmium can lead to skeletal dysplasia and osteoporosis by interfering with calcium metabolism. The development of otolith in vertebrates is similar to that of bone, but the related regulatory factors and processes are different. Although more data on cadmium toxicity have been accumulated, the toxic effects and mechanisms of cadmium on otolith development are not yet clear. The influence of maternal exposure on the development of fetal otolith is not clear, too. Therefore, the following research is carried out with zebrafish as a model: 1), the influence of environmental related dose of cadmium exposure on otolith development, and the mechanism of action, as well as the impact on early physiological activities, such as swimming balance and other behavioral changes. 2), the effects of parental cadmium exposure on the development of the otolith in the offsprings, and the response of the related developmental factors to cadmium exposure in the parent and progeny. By carrying out the research above, we expect to provide experimental evidence for evaluating the toxicity of the cadmium exposure on otolith development in vertebrates, and provide an important basis for evaluating the potential harm of maternal cadmium exposure to the otoliths development in the offsprings.

镉是环境毒理学重点研究的重金属元素。在电子垃圾拆解地、重金属矿区等地，环境化学分析揭示了镉暴露的普遍性和潜在风险，尤其母代孕期和新生个体早期发育阶段受暴露程度较为严重。镉通过干扰钙代谢导致骨骼发育不全、骨质疏松等毒性效应。脊椎动物耳石发育与骨骼类似，但相关调控因子及过程不同。尽管目前积累了较多镉毒性数据，但镉对耳石发育的毒性效应和机制尚不清楚，母代暴露对胎儿耳石发育的影响也尚不明确。因此，本课题以斑马鱼为模型开展以下研究：1. 环境相关剂量的镉暴露对耳石发育的影响和作用机制，以及对早期生理学活动的影响，如游泳平衡等行为学变化。2. 母代镉暴露对子代耳石发育的影响，并探讨母、子代耳石发育相关因子对镉暴露的响应。以期通过开展上述研究，为评价镉暴露导致的脊椎动物耳石发育毒性提供实验证据，为评价母代镉暴露对子代耳石发育的潜在危害提供重要依据。

镉是环境毒理学重点研究的重金属元素。环境化学分析和前期毒理学研究揭示了镉暴露的普遍性和潜在健康风险。镉主要通过干扰钙代谢导致骨骼发育不全、骨质疏松等毒性效应。耳石对脊椎动物保持机体平衡等方面具有十分重要的生理学意义。脊椎动物耳石发育与骨骼类似，但相关调控因子及过程不同。尽管目前积累了较多镉的毒理学数据，但镉暴露对脊椎动物耳石发育等生物矿化过程的毒性效应和机制尚不清楚。本项目以氯化镉为例，以斑马鱼仔鱼和成鱼为动物模型，采用生物学、分子生物学、生物化学、分析化学等相关技术手段，评价了环境剂量镉污染对鱼类（特别是早期生命阶段）耳石、骨骼发育等生物矿化过程的毒性效应，揭示了不同生物矿化过程受影响的分子机制，以及对外源钙离子水平变化的响应等。具体发现，环境浓度水平的镉暴露能够通过干扰体内钙离子代谢来抑制斑马鱼仔鱼的耳石发育过程，进而干扰其游泳平衡及速度等运动行为；镉暴露显著抑制了仔鱼鳃条骨和椎骨的矿化过程，而同等剂量水平下对成鱼耳石、椎骨和臀鳍矿化过程无显著影响；镉暴露显著干扰了仔鱼代谢相关通路，特别是导致了脂质代谢异常；暴露水环境中钙离子浓度水平升高可以消除以上毒性效应。该结果为镉暴露对鱼类等脊椎动物的耳石发育等生物矿化过程的影响提供了重要科学依据，为综合评价水体重镉污染对水生生物的环境健康风险提供了重要参考，为镉的水生生物基准和相关标准的制定提供了数据支撑。