裸燕麦β-葡聚糖对血脂异常的调控作用：以肠道菌群为靶点的机制研究

Dyslipidemia has now become a major public health concern as it predisposes to a number of chronic diseases.Accumulating evidences have indicated that gut microbiota might be associated with the etiology and development of dyslipidemia,yet the exact relationship between gut micorbiota and dyslipidemia is still controversial. Furthermore, the feasibility of prevention and treatment of dyslipidemia via adjusting the intestinal flora has to be further explored.Oat is one of whole grains with the useful life activities and physiological role. Oat β-glucan has been demonstrated to be clinically effective in lowering serum lipids, yet the mechanisms are still not entirely clear. On the other hand, the reseach about oats lowering blood lipid was mainly concentrated in the normal oats, while the relationship between naked oats and intestinal flora and dyslipidemia is unavalible. This program aims to investigate the lipid-lowering effect and mechanisms of naked oat β-gluca based on gut microbiota.The combination of the metagenomic and metabolomic approaches would offer a powful tool for the elucidation of underlying metabolic interactions between the gut micorbiota and its host and ultimately to elucidate the relationship between oat β-gulcan and dyslipidemia. The results of this research will provide strategy for the prevention and treatment of dyslipidemia from the diet and theoretical basis and technical support.

近年来血脂异常的发病率持续增长，已成为重要的公共卫生问题。研究发现，肠道菌群在血脂异常的发生发展过程中发挥着重要的作用，为血脂异常的防治策略探索提供了新方向。但肠道菌群与宿主脂代谢的具体互作关系尚未明确，通过调整肠道菌群防治血脂异常的策略也有待进一步系统探索。燕麦具有独特的营养价值和保健功能，燕麦β-葡聚糖的降脂功效也已得到公认，但其降脂的具体功效机制尚不明确。我国是裸燕麦的发源地和主产国，而目前有关燕麦降血脂的功能研究主要集中在皮燕麦，尚未见关于裸燕麦与肠道菌群及血脂异常关系的报告。本项目拟从肠道菌群入手，以高脂饮食喂养金黄地鼠构建血脂异常动物模型，观察不同剂量裸燕麦β-葡聚糖的降脂作用和剂量功效关系，从器官、肠道菌群、基因表达等多方面探索其调控机制，并确定特征性功能菌属和可能功效途径，从营养干预角度为血脂异常的防控提供理论和策略依据。

本研究以高脂饮食喂养金黄地鼠构建血脂异常动物模型，将实验动物分为正常对照组、正常干预组、高脂对照组、高脂干预组、模型对照组、燕麦β-葡聚糖低、中、高剂量组和高脂预防组，连续喂养10周，每天观察金黄地鼠的大鼠生长、进食及活动情况，于第0、45、90天内眦取血进行血脂等血清学测定，留取新鲜粪便进行细菌培养及肠道菌群检测。采用western blotting和免疫组化法检测肝脏和小肠组织中炎症相关蛋白的表达情况。GC-TOF-MS 技术分析血清代谢物组，分析与血脂异常和燕麦β-葡聚糖干预相关的差异代谢物，并进行代谢通路探索。结果显示：燕麦β-葡聚糖干预可有效调节血脂异常金黄地鼠的血脂和体重水平，并可改善肝脏及肠道的形态和功能。高脂饮食引起肠道菌群结构失衡，燕麦β-葡聚糖可使其得到一定程度的缓解。多变量统计分析结果显示肠道菌群与炎症指标和代谢组学指标均有着密切的关系，提示肠道菌群可能在机体炎症反应和代谢中有着重要作用，燕麦β-葡聚糖可以通过调节肠道菌群发挥调脂和抗炎作用。本研究结果为燕麦β-葡聚糖作为防治血脂异常的临床营养辅助治疗提供一定的科学依据，同时为寻求安全有效的防治方案提供了理论依据。