基于海南候鸟人群研究NAIs通过BER途径调节高血压的作用及分子机制

高血压是全球死亡的第一位危险因素，其发生发展受环境和遗传因素的综合影响。研究表明NAIs具有降压等作用，海南空气中NAIs浓度较高，被誉为“天然氧吧”，8-OHdG水平作为预测高血压疾病发展的生物标志物之一，可被BER途径中的关键限速酶hOGG1和APE1特异性修复，且其修复能力受到hOGG1 Ser326Cys和APE1 Asp148Glu位点多态的影响。因此，本项目拟选取一组（约244例，男女各半）计划从东北三省迁移到海南，在海南连续居住≥0.5年、年龄≥50岁且患有高血压的候鸟人群为研究对象开展前瞻性定组研究，共进行三阶段访视（东北2021年8-9月和海南2021年10-11月、2022年3-4月，各一周），人群结果构建混合效应模型，结合动物实验，共同探讨NAIs浓度变化对血压、体格指标、氧化应激水平、DNA损伤修复水平的影响，为NAIs改善人群高血压的作用及其分子机制提供理论依据。

Hypertension is the leading cause of death and disability worldwide and influenced by the combination of genetic and environmental factors. Hainan is known as "natural oxygen bar", and the high concentration of negative air ions (NAIs) has the function of depressing blood pressure. High levels of 8-OHdG, a biomarker for predicting hypertension, can specifically repaired by base excision repair (BER). Human 8-oxoguanine DNA glycosylase-1 (hOGG1) and Apurinic apyrimidinic endonuclease (APE1) are the key genes in BER. Research shows that DNA repair ability is the important factor to influence hypertension and DNA repair ability is closely related with single nucleotide polymorphisms (SNPs). hOGG1 gene Ser326Cys polymorphisms and APE1 gene Asp148Glu polymorphisms are associated with an individual's ability to repair oxidative damage. Therefore, we select Hainan “migratory birds” as our panel researchers, who aged ≥50 years and suffering from hypertension, and plan to migrate from the three provinces in the northeast of China to Hainan and live in Hainan continuously for ≥0.5 years. Linear mixed-effects models are established by the data of panel study results. The combination of population study and rat experiment can be explored the effects of NAIs on blood pressure, physical indicators, oxidative stress level and DNA damage repair capacity. It will provide powerful evidence for molecular mechanism of negative oxygen ions in regulating hypertension through BER pathway.