膳食及体内植物化学物对中老年人氧化应激、炎性反应和动脉粥样硬化影响的前瞻性研究

Atherosclerosis (AS) is closely related to nutritional/dietary and genetic factors. In vitro studies showed that oxidative stress and inflammation play a key role in the developing and progress of AS. However, up to date, no large prospective study has examined the overall effect of multiple oxidantive phytochemicals and polymorphisms of candidate genes in Chinese populations. To address this issue, we proposed this study based on a community cohort of 3084 Guangzhou residents (40-75y) established during 2008-2010, subjects completed baseline survey and will complete two follow-ups during 2011-2013 (~2500 subjects) and 2014-2016 (~2100 subjects). Nutritional and dietary factors would and will be collected using food frequency questionnaire and blood or 24-h urinary analyses. Dietary consumption of common phytochemicals and blood or urine concentrations of phytochemicals were/will be assessed at baseline and the followups. Blood inflammatory cytokines and oxidative/anti-oxidative factors at each visity will be determined. Gene polymorphisms related to some inflammatory cytokines and anti-oxidative enzymes will be assessed. The intima-media thicknesses (IMTs) will be determined via B-mode ultrasound with a high-resolution, 7.0-12.0 MHz linear-array transducer system (Aplio TOSHIBA, Japan) in the far walls of three main segments of the right and left extracranial carotid arteries, including the common carotid artery (CCA), bifurcation (BIF) and internal carotid artery (ICA). The associations of various phytochemicals and other nutritional and dietary factors, blood inflammatory cytokines and oxidative/anti-oxidative factors, and the polymorphisms of their related candidate genes with the changes in IMT and risk of AS will be determined using univariate and multivariate analyses. Predictive model of phytochemical-based nutritional/dietary factors will be established for the prediction of the changes in IMT and risk of AS, and these results will provide the scientific evidence for making the dietary guideline for the AS prevention in Chinese. To address the potential mechanism of AS, path analysis will be used to determine the role of oxidative stress and inflammatory cytokines in the causal chain between phytochemicals and other dietary factors and IMT and risk of AS. Interaction analyses of phytochemicals and genes will be conducted to identify the susceptibility genes, and these results will form the foundation for individualized measures of AS prevention via dietary approach.

体外实验提示氧化应激与炎性反应为动脉粥样硬化（AS）重要原因。植物化学物（FC）是膳食重要的抗氧化因素，然而迄今我国尚无大样本前瞻性研究来验证和比较不同FC与多基因对AS的影响以及氧化应激与炎性反应在其中所起的作用。为此，本研究拟利用我院同事2008-10年建立的3千名40-75岁广州社区居民队列，通过基线及11-13年与14-16年两次随访调查共6年的前瞻性研究，分析膳食及血尿FC、炎性反应及氧化应激水平，炎性因子与抗氧化酶相关基因多态性等因素与颈动脉内中膜厚度（IMT）变化及AS发病风险的关联。验证及比较不同的FC对AS的影响；建立对IMT变化及AS预测的以FC为主体营养膳食模型，为制订AS膳食防治措施提供科学依据；检验氧化应激及炎性反应是否为营养膳食因素影响人群AS的关键环节以阐明作用机制；通过营养与基因交互作用分析，筛查具有调节作用的相关基因型，为我国AS个体化干预提供科学依据。

体外实验提示氧化应激与炎性反应为动脉粥样硬化（AS）重要原因。植物化学物（FC）是膳食重要的抗氧化因素，然而迄今我国尚无大样本前瞻性研究来验证和比较不同 FC 与多基因对 AS 的影响以及氧化应激与炎性反应在其中所起的作用。为此，本研究利用我院同事已建立的社区居民队列，进行第二次随访，分析FC与氧化应激及炎性反应水平等相关因素与颈动脉内中膜厚度（IMT）及 AS 发病风险的关系，为制订AS 膳食防治措施提供科学依据。研究结果显示，男性双侧颈总动脉及分叉段内中膜厚度均高于女性；单变量和多变量分析结果显示，被测人群的血清类胡萝卜素浓度与颈动脉各段平均内中膜厚度呈反向剂量依赖关系，膳食类胡萝卜素的摄入（番茄红素除外）可对颈总动脉内中膜厚度起到显著的保护作用；膳食总类胡萝卜素的主要食物来源分别是深绿色蔬菜（44.7％）、胡萝卜、辣椒和西红柿（21.2％）、瓜茄类蔬菜和小红萝卜（20.2％）、总水果（7.89％）。此外，基于本项目的研究基础和进展，已完成100多种食品（包括水果、蔬菜、谷物和蘑菇）中几种植物化学物的含量测定，并改进了血液中多种植物化学物的测定方法，该方法节约了大量的测定时间（每个样品的测定时间从2小时缩短为20分钟），提高了灵敏度和可靠性。培养了多名硕士和博士研究生，其中4人获得“国家研究生奖学金”，5人获得“中山大学优秀研究生”荣誉称号。发表了多篇SCI论文，并得到广泛引用，项目负责人也入选“2017年全球高被引用科学家”。