基于单细胞测序技术探讨聚苯乙烯微塑料诱导肝脏脂质代谢异常的作用机制

微塑料是新型的环境污染物，聚苯乙烯微塑料(PS-MPs)是其中最为常见的一种。PS-MPs的暴露会导致多种生物模型出现肝脏脂质蓄积的毒性效应。以往研究发现：肝脏微环境中各类细胞的交互作用在肝脏疾病发生发展过程中具有重要的意义，但在环境污染物例如PS-MPs诱导的肝脏脂质代谢异常过程中分别扮演了什么角色则未见报道。本项目拟建立PS-MPs诱导的小鼠肝脏脂质代谢异常模型，并通过单细胞转录组学测序技术及生物信息学分析等手段了解从PS-MPs暴露到出现肝脏脂质蓄积过程中不同细胞类型的响应、脂质代谢相关信号通路及基因的动态变化，筛查与PS-MPs暴露相关的敏感靶细胞亚群以及作用靶点，利用体外细胞模型验证PS-MPs作用的关键靶点和毒性通路，揭示其诱导肝脏脂质蓄积的分子机制。最终通过动物模型及细胞模型的实验数据获得基准剂量参考值（BMD），为PS-MPs的安全限值制定及风险评估提供科学依据。

Microplastics are a new type of environmental pollutants, and polystyrene microplastics (PS-MPs) are the most common one. Exposure to PS-MPs can cause toxic effects of liver lipid accumulation in various biological models. Previous studies found that the interaction of various cells in the liver microenvironment is of great significance in the development of liver disease. However, their roles in the abnormal metabolism of liver lipids induced by environmental pollutants such as PS-MPs have not been elucidated. This project intends to establish a model of abnormal liver lipid metabolism in mice induced by PS-MPs, and then, single-cell transcriptomic sequencing and bioinformatic analysis will be used to explore the response of the different hepatic cell types with lipid metabolism-related signaling pathways and genes, thus screening for sensitive cell subsets and targets related to PS-MPs exposure. The in vitro hepatocyte model will be used to verify the key targets and toxicity pathways affected by PS-MPs and reveal the mechanism of liver lipid accumulation mediated by PS-MPs. The benchmark dose (BMD) will be obtained from the experimental data of animal models and cell models, which could provide a scientific basis for the establishment of safety limits and risk assessment of PS-MPs.