膳食高磷在有氧运动改善冠心病预后中的作用及机制研究

Coronary heart disease (CHD) and its increasing incidence is an important public health problem in China. Because of its complicated pathogenesis and clinical heterogeneity, there’s still lack of efficient strategies for preventing CHD. Nutrition and physical exercise are considered to be the most efficient prevention for CHD. Previous epidemiological studies indicated that high phosphorus intake is one of the independent risk factors of CHD. According to previous animal studies, high phosphorus intake inhibited the effects of aerobic exercise on improving heart dysfunction. However, the effects and the underlying mechanism of the combined effect of nutrition and exercise are lack of studying. This study aims to investigate the effect of dietary phosphate intake on the improvement of CHD prognosis by aerobic exercise in Guangdong coronary artery disease cohort study, and explore the effect of high dietary phosphate intake on heart function and the effectiveness of aerobic activity by using apoE knockout mice; and further explore the potential mechanisms among high phosphorus, myocardium dysfunction and reduced exercise effectiveness, which in order to explore the effect of interaction between imbalance nutrition and exercise on the prognosis of CHD, providing new targets and scientific basis for the combined lifestyle intervention of cardiovascular diseases.

冠心病持续高发已成为我国重大公共卫生问题。由于其致病机制复杂、临床异质性高，至今仍缺乏有效的防治干预措施。营养膳食和运动被认为是冠心病最有效的防治策略。流行病学研究提示，高磷摄入是冠心病不良预后的独立危险因素；动脉粥样硬化小鼠模型研究指出，高磷膳食显著降低有氧运动对心功能的改善。然而，膳食磷摄入与运动干预协同改善冠心病预后的作用及其分子机制至今尚未阐明。本研究拟在已建立的广东省冠心病患者队列中探索膳食磷摄入量在运动改善冠心病不良预后中的作用；在apoE基因敲除小鼠模型中探讨高磷膳食拮抗运动改善心功能、延缓斑块形成的效应；并进一步在细胞模型中，全面深入探讨高磷调节心肌能量代谢降低运动获益的分子机制。本研究将首次从营养失衡降低运动改善冠心病预后效力的角度阐释膳食均衡及运动干预在心血管病防治中的协同效应，为冠心病的早期防治和改善不良预后提供科学依据。研究结果将为心血管病的早期联合干预提供新思路。

随着生活方式变迁和老龄化加剧，冠心病的发病率和患病率持续攀升，高居我国城乡居民总死亡原因第二位，已成为严重危害国民健康的重大公共卫生问题。以均衡膳食、适量运动为主的生活方式干预被认为是改善冠心病最有效的措施。随着膳食结构的西化，尤其是食品添加剂和增味剂等使用的增加，我国居民膳食磷摄入已远远超过其推荐摄入量。本项目以血清磷作为评价膳食磷摄入的指标，基于前瞻性队列研究，明确了血清磷水平升高与冠心病患者远期死亡风险增加密切相关，是冠心病不良预后的独立危险因素。通过分析发现，肝纤维化评分、血清镁、血清钙/镁比、血浆神经酰胺水平和胰岛素抵抗代谢评分与冠心病发生发展密切相关。实验结果显示，高磷膳食干预显著降低有氧运动抑制动脉粥样硬化斑块形成的作用。本项目首次从膳食磷摄入不均衡降低有氧运动改善冠心病效力的角度探讨合理膳食及有氧运动干预在冠心病防治中的联合作用，研究结果为冠心病生活方式管理提供新的靶标及科学依据，对防治心血管疾病、减轻疾病负担具有重要现实意义。