有机磷酸酯心血管毒性效应识别与毒性作用机制研究

心血管疾病如高血压、动脉粥样硬化等已成为全球面临的重大公共卫生问题。其成因复杂，除了年龄和遗传因素外，多种环境因素如污染化学物质暴露等也被认为是导致心血管疾病的重要风险因子。本项目以揭示有机磷酸酯类物质的心血管毒性效应和毒性作用机制作为研究目标，通过建立基于图像识别技术的斑马鱼胚胎心血管毒性效应自动化高通量高内涵筛选方法，系统性评估有机磷酸酯类物质的心血管毒性效应潜能，阐明其潜在的毒性作用靶点；通过开展斑马鱼胚胎暴露实验，明确典型有机磷酸酯对斑马鱼心血管系统发育功能、组织形态及生理生化水平的影响，并从细胞和分子水平阐明其心血管毒性作用分子机制；在此基础上，结合小鼠暴露实验，初步厘清典型有机磷酸酯对啮齿动物模型心血管系统发育与功能的影响，从而为准确评估该类物质的毒理学效应和健康风险提供科学依据，并为有效的心血管疾病防治工作提供一定的科学支撑。

Cardiovascular diseases such as hypertension and atherosclerosis have become major public health issues. In addition to age and genetic risk factors, various environmental risk factors such as environmental pollutions have been implicated. The project focuses on the cardiovascular toxicities and related mechanism of actions of the organophosphate flame retardants (OPFRs). By establishing and optimizing the image recognition based high-throughput high-content screening methods in zebrafish model, the cardiovascular effects of OPFRs will be systemically evaluated and prioritized. The effects of prioritized OPFRs on cardiovascular functions and related histological, physiological and biochemical alterations will be further demonstrated. The underlying molecular mechanisms will be explored. In addition, the BALB/c mice model will be further employed to illustrate the effects of OPFRs on the cardiovascular system of rodents. The results from this project will provide scientific evidences for the risk assessment of OPFRs and will be helpful on the effective prevention and treatment of the cardiovascular diseases.