miR-200家族及其靶基因多态性在职业性噪声暴露致心血管早期损伤中的作用研究

Noise is one of the most common occupational hazards in China. It is revealed that long-term exposure to occupational noise could increase the risk of early cardiovascular injury; however, the underlying mechanism is unclear. Recent studies have shown that the miR-200 family plays an important role in the development of early cardiovascular injury, but the potential role of miR-200 family was never investigated in the pathogenesis of early cardiovascular injury caused by exposure to occupational noise. Our study was conducted based on the occupational noise cohort population, the noise intensity and frequency, the cumulative noise exposure and the expression level of plasma miR-200 family were measured and evaluated, and blood pressure, blood glucose, blood lipids, heart rate variability and arterial stiffness were used as outcome variables, we aimed to examine the association between occupational noise and early cardiovascular injury, and the mediate effect of miR-200 family between them. In addition, we also explore the interaction effect of occupational noise, miR-200 family and the polymorphism of its target gene through testing the polymorphism of the five candidate sites of SORT1. The results could provide clues for the mechanism of early cardiovascular injury caused by exposure to occupational noise.

噪声是我国目前最主要的职业有害因素之一，长期暴露于职业性噪声可增加心血管早期损伤的风险，但其致病机制尚未完全阐明。最新研究表明，miR-200家族在心血管早期损伤的发生中起着重要作用，但其在职业性噪声致心血管损伤中的作用尚未见报道。本项目依托于前期建立的职业性噪声接触工人队列，通过测量和评估研究对象接触的噪声强度、累积噪声暴露量和岗位频谱噪声，测定血浆miR-200家族的表达水平，以血压、血糖、血脂、心率变异和动脉硬化作为心血管早期损伤的效应指标，探讨职业性噪声暴露（累积噪声暴露量、噪声暴露频率）与心血管早期损伤的关联性，以及miR-200家族在职业性噪声暴露致心血管早期损伤中的中介作用；同时通过对其靶基因SORT1的5个候选位点多态性进行分型检测，进一步研究职业性噪声、miR-200家族及其靶基因多态性的交互作用对心血管早期损伤的影响，为明确职业性噪声暴露致心血管早期损伤的机制提供依据。

噪声是我国目前最主要的职业有害因素之一，长期暴露于职业性噪声可增加心血管早期损伤的风险，但其致病机制尚未完全阐明。最新研究表明，miR-200家族在心血管早期损伤的发生中起着重要作用，但其在职业性噪声致心血管损伤中的作用尚未见报道。本项目依托于职业性噪声接触工人队列，通过测量和评估研究对象接触的噪声强度和累积噪声暴露量，测定血浆miR-200家族（miR-200a、miR-200b、miR-200c、miR-141和miR-429）和另外3种miRNAs（miR-1、miR-92a和miR-21）的表达水平，以血压、血糖、血脂、心率变异和动脉硬化作为心血管早期损伤的效应指标，探讨职业性噪声暴露与心血管早期损伤的关联性，以及miRNAs在职业性噪声暴露致心血管早期损伤中的中介作用。研究发现，职业性噪声暴露与动脉硬化（baPWV），心率变异（SDNN, SDNN index和HF），血压（收缩压和舒张压）和血脂（HDL-C）存在一定的关联性；此外，我们同时发现职业性噪声暴露与其中5种miRNAs（miRNA-200c-3p，miRNA-200a-3p，miRNA-200b-3p，miRNA-92a-3p和miRNA-21-5p）存在一定程度的关联。最后，我们发现部分miRNAs中介了职业性噪声暴露与心血管早期损伤的关联性，其中miR-92a-3p和miR-21-5p部分中介了职业性噪声暴露与动脉硬化（baPWV）之间的关系，其中介比例分别为15.0%和16.8%；miRNA-92a-3p中介了职业性噪声与舒张压的关系，其中介比例为24.66%。本项目的研究结果可以为明确职业性噪声暴露致心血管早期损伤的机制提供依据。