ABCD4在辐射诱导心血管损伤中的作用及其机制研究

核与辐射安全与人群心血管健康的关系以往常被忽视，缺乏系统研究。目前，流行病学研究认为核与辐射会诱发心血管疾病增加，且我国核工业、核电及医疗等放射工作人群快速增长，辐射对该人群的健康影响不容小觑。核与辐射诱导心血管损伤基因、分子、靶点，以及低剂量辐射与缺血性心脏病的关系等重大科学问题尚待探索，应加以证实。ABCD4是溶酶体膜蛋白之一，维持细胞稳态及功能。我们首次发现低剂量辐射暴露人群ABCD4在不同剂量照射下显著低表达，且存在剂量依赖性，人群数据进一步显示辐射可增加心血管损伤风险。本项目将在此基础上，通过构建ABCD4过表达和基因沉默载体及实验动物模型，从分子、细胞、动物、人群等角度深入探讨ABCD4在辐射诱导心血管损伤中的作用及其机制。研究结果不仅可揭示ABCD4与辐射诱导心血管损伤的变化规律，还可为放射工作人员心血管损伤的防控和干预措施提供新线索、新思路。

It was formerly ignored and lacked of research that the relationship between radiation safety and cardiovascular health in the past. At present, it was believe that nuclear radiation may increase cardiovascular diseases from epidemiological studies, and with the rapidly growing of nuclear industry and nuclear power’ persons, it cannot be underestimated on human health effects from radiation. So it is extremely necessary to carry out relevant research. There major scientific issues, from radiation-induced cardiovascular damage related genes, molecules, targets, and the relationship between LDIR and ischemic heart disease, remain to be explored and confirmed. ABCD4, maintaining cell homeostasis and function, is one of the lysosomal membrane proteins. We found firstly that the expression of ABCD4 mRNA in the low-dose ionizing radiation exposure staffs was significantly reduced with a dose-dependent manner. The results of further preliminary experiments strongly prompt that ABCD4 is related to cardiovascular radiation damage. Base on this basis, this project will deeply explore the role and mechanism of ABCD4 in radiation-induced cardiovascular damage from multiple levels based on building ABCD4 overexpression and gene silencing vectors and experimental animal models. The research results can not only reveal the changing discipline of ABCD4 and radiation-induced cardiovascular injury, but also provide new clues and ideas for radiation workers' cardiovascular injury prevention and control and intervention measures.