尿液雌马酚对动脉粥样硬化的影响及相关机制：12年随访研究

Animal experiments have shown that soy isoflavones (SI) have the potential effects to prevent atherosclerosis (AS) and its related risk factors, but there was great divergence in the results of population epidemiological studies. It has been pointed out that the higher biological activity of SI metabolite-equal may be the key factor for SI to play a beneficial role. However, only some people can produce equal through metabolism of human gut microbiota after intake of SI. Previous studies have rarely distinguished whether or not subjects of studies produced equal, which may be an important reason for the difference in the results of the SI efficacy study. Up to date, no prospective study with large sample has verify this association. To address this issue, we will propose this study based on "Guangzhou Nutrition and Health Study" with 4048 middle-aged and elderly people recruited from 2008. Subjects who completed baseline survey will complete four follow-ups with a total of 12-year follow-up (visited every 3 years). In this study, nutritional and dietary factors would and will be collected using food frequency questionnaire. Dietary consumption of SI were/will be assessed at baseline and the follow-ups. Fasting blood, morning urine and fecal sample would/will be collected. Blood oxidative/anti-oxidative factors and inflammatory cytokines have been determined. The intima-media thicknesses (IMTs) were/will be determined via B-mode ultrasound with a high-resolution, 7.0-12.0 MHz linear-array transducer system in the far walls of two main segments of the right and left extracranial carotid arteries, including the common carotid artery (CCA) and bifurcation (BIF). We will analyze the relationship of urine equal level with carotid artery intima-media thickness (IMT) changes and risk of AS for verifying whether equal is the key factor to determine the effect of SI on AS. We will also test that whether the level of oxidative stress and inflammation are the key links of the influence of equol on AS, in order to clarify the mechanism of action. Meanwhile, the effects of gut microbiota on the level of equol in vivo will be analyzed. The structures or patterns of the gut microbiota which are beneficial to the production of equol will be explored, in order to promote the production of the equol through intervening that patterns of gut microflora, or promote synthesis of equol as a kind of health care product through an appropriate microbiota mode in vitro.

大豆异黄酮（SI）潜在预防动脉粥样硬化（AS）及其相关危险因素的作用存在显著人群差异，目前仍原因未明。雌马酚作为SI经肠道菌群代谢的产物被认为生物学活性最高，可能是SI的有效作用成分，且仅在部分人群中代谢产生，然而迄今尚无大样本前瞻性队列研究验证雌马酚对AS的作用。为此，本研究基于2008年起建立的4,048名中老年人队列，每三年随访一次，通过基线和四次随访共12年的资料和样本收集，分析多次检测的随访尿液雌马酚平均水平、氧化应激及炎性反应水平与B超检查颈动脉内中膜厚度变化、AS发病风险的关联；同时分析肠道产雌马酚菌种丰度、菌群模式及多态性与雌马酚水平的相关性。前瞻性地阐明雌马酚对AS发生发展的影响及相关作用机制，检验雌马酚是否为SI的有效作用成分之一，并探索有利于雌马酚产生的菌群结构或模式，为干预肠道菌群模式促进雌马酚的产生或体外通过适宜菌群模式合成雌马酚提供科学依据。

大豆异黄酮（SI）潜在预防动脉粥样硬化（AS）及其相关危险因素的作用存在显著人群差异，目前仍原因未明。雌马酚作为SI经肠道菌群代谢的产物被认为生物学活性最高，可能是SI的有效作用成分，且仅在部分人群中代谢产生，然而迄今尚无大样本前瞻性队列研究验证雌马酚对AS的作用。为此，本研究基于2008年起建立的4,048名中老年人队列，每三年随访一次，通过基线和四次随访共12年的资料和样本收集，分析多次检测的随访血清和尿液雌马酚水平、炎性反应水平与B超检查颈动脉内中膜厚度（IMT）变化、AS发病风险的关联；同时分析肠道产雌马酚菌种丰度、菌群模式及多态性与雌马酚水平的相关性。结果发现，血清异黄酮和雌马醇暴露与IMT进展减少相关，且该通路由性激素结合蛋白和收缩压介导。非产雌马酚者与产雌马酚者的微生物群落物种丰富度和肠道微生物群落β多样性有显著差异。该研究在理论上可以丰富大豆异黄酮的代谢产物对 AS 及其相关危险因素影响的相关理论知识。实际应用上，通过探索肠道微生物中影响雌马酚产生的特定菌种与菌群模式，为体外通过适宜菌群模式合成雌马酚作为保健品开发提供科学依据，为心血管健康指导提供证据。

内容获取失败，请点击重试