渤海重金属污染物镉对菲律宾蛤仔剂量-响应关系与机制研究

近年来的调查研究表明镉是渤海生态风险最高的重金属污染物。申请人课题组前期利用代谢组学结合细胞与分子生物学方法，证实环境相关浓度的镉对渤海代表性生物类群沙蚕与菲律宾蛤仔同时存在显著的单调与双相剂量-响应关系，提示研究者须全面阐释镉的剂量-响应关系，避免歪曲解释镉的毒理效应，以及筛选出假阳性生物标志物。本项目针对渤海镉污染现状，拟在前期研究基础上，开展镉对菲律宾蛤仔剂量-响应关系及其机制的创新性研究：应用对数线性插值法，通过血细胞凋亡率，在细胞水平确定镉对蛤仔双相剂量-响应关系的浓度范围；整合利用转录组学、代谢组学与离子组学技术，从蛤仔渗透调节、离子稳态及分子水平的响应信息，深入阐明镉对蛤仔剂量-响应关系的作用机制，并在分子水平确定镉对蛤仔双相剂量-响应关系的浓度范围及阐明代谢通路；结合生物信息学与统计学方法，筛选单调剂量-响应的分子生物标志物，为渤海镉污染的生物监测和风险评估提供有力工具。

Recent researches have confirmed that cadmium (Cd) is the main heavy metal pollutant with the highest ecological risk in the Bohai Sea. Based on the funding from NSFC, our research group evidenced that environmentally relevant concentrations of Cd could significantly induce both monotonic and biphasic dose responses in two bioindicators, polychaete Perinereis aibuhitensis and clam Ruditapes philippinarum, in the Bohai Sea, using metabolomcis combined with cytobiology and molecular biology. These findings remind researchers of focusing on the dose responses induced by Cd in marine organisms, which may avoid distorting the interpretation of toxicological effects and false positive biomarkers. On the basis of our recent investigations, this project will focus on the Cd pollution in the Bohai Sea to carry out exploratory investigations on the dose responses and mechanisms induced by Cd in clam R. philippinarum. After testing the apoptotic cell rate of haemocytes collected from clams, we will determine the concentration range of biphasic dose responses induced by Cd at cellular level, using linear interpolation on the log concentration scale. Subsequently, multi-omic techniques, including transcriptomics, metabolomics and ionomics, will be integrated to characterize the dose responsive mechanisms related to Cd-induced effects in osmotic regulation and ion homeostasis in clams. At molecular level, furthermore, the concentration range of biphasic dose responses will be determined by linear interpolation on the log concentration scale and corresponding fingerprints of metabolic pathways will be constructed based on the transcriptomic and metabolomic responses induced by Cd in clams. In addition, the monotonic responsive biomarkers of Cd will be selected using bioinformatics and statistics, such as linear regression analysis and Pearson correlation analysis, which may hopefully provide a useful tool for biomonitoring and risk assessment of Cd in the Bohai Sea.