TnC/TPM4信号通路在氚水诱导心脏发育异常中的调控作用

近年来，公众越来越关注环境中电离辐射暴露引起的健康问题和环境影响。在环境放射性核素暴露中，最主要的核素之一是氚。随着核能事业的不断发展, 核反应堆的建立日益增多，氚向环境中排放量将不断增加，明确氚暴露对人类健康及环境生态的影响迫切而必要。课题组前期实验发现：氚水暴露后，斑马鱼心率增加、活动降低，tnnc1a基因表达增加。由此提出科学假说：氚水通过上调TnC/TPM4信号通路导致心脏发育异常。本课题拟建立斑马鱼和离体心肌细胞氚水染毒模型，采用RNA干扰、免疫荧光、western blot、Co-IP、RT-PCR等技术，检测斑马鱼心脏发育毒性、tnnc1a和TPM4基因表达、蛋白表达、蛋白共定位等，从而阐明TnC/TPM4信号通路参与氚水诱发心脏发育毒性的功能和机制。本课题的完成不仅为氚水损伤防护提供新的分子靶点，还为氚水的环境暴露生态风险评估提供数据，具有重要的理论意义和社会价值。

In recent years, the public has paid more and more attention to the health problems and environmental impact caused by ionizing radiation exposure in the environment. Tritium is one of the most important nuclides in environmental radionuclide exposure. With the continuous development of nuclear power industry, the establishment of nuclear reactors is increasing, and tritium emissions to the environment will continue to increase. It is urgent and necessary to clarify the impact of tritium exposure on human health and environmental ecology. The preliminary experiment of the research group found that after tritiated water exposure, zebrafish heart rate increased, activity decreased, and tnnc1a gene expression increased. It is suggested that tritiated water can up regulate the signal pathway of TnC / TPM4 and lead to cardiac dysplasia. The purpose of this study is to establish a tritiated water toxicity model of zebrafish and isolated cardiomyocytes. RNA interference, immunofluorescence, Western blot, CO IP, RT-PCR and other techniques were used to detect the cardiac developmental toxicity of zebrafish, tnnc1a and tpm4 gene expression, protein expression, protein co-localization and so on, so as to clarify the function and mechanism of TnC / TPM4 signal pathway involved in tritiated water induced cardiac developmental toxicity. The completion of this project not only provides a new molecular target for tritiated water damage prevention, but also provides data for the ecological risk assessment of tritiated water environmental exposure, which has important theoretical significance and social value.