基于“肠道-TLR4/NFκB-炎症”野菊花黄酮抗“过食肥甘醇酒”致代谢性高血压机制研究

Hypertension is one of the most common cardiovascular diseases that endanger human health seriously with involving severe serious complications such as heart, brain, kidney, eyes and so on. The formation of metabolic hypertension is due to the unreasonable dietary patterns such as “over-diet fat and alcohol”, and this way will lead to imbalance of intestinal flora and intestinal barrier dysfunction, formation of systemic mild chronic inflammation, and the vascular structure and function of the body damage, insulin resistance, water and sodium retention and abnormal activation of RAAS. Chinese medicine believes that the body "in the full heat caused by heat toxic. Now it has been the main body of hypertension. Chinese medicine believes that “over-diet fat and alcohol” will cause the body in“heat poisoning” of “heat in the full body”. At present, the use of chemical drugs alone is not ideal and requires lifelong medication. Flos Chrysanthemi Indici has the function of clearing heat and detoxifying the detoxification and the effect of anti-hypertensive effect. Previous studies have made clear the optimal ratio of the anti-hypertensive components of flavonoids from Flos Chrysanthemi Indici, which can regulate the inflammatory factors and inhibit the inflammation of vascular cells induced by LPS. This topic will use modern techniques and other means to study the Flos Chrysanthemi Indici on the intestinal flora, intestinal barrier function, LPS levels and activation related signaling pathways, inflammatory responses, and the effects of it on vascular function, insulin resistance, RAAS, SNS and so on are to be observed. The mechanism and characteristics of flavonoids from Flos Chrysanthemi Indici on hypertension were expounded, which lay the foundation for the development of new anti-hypertensive drugs and the full utilization of Flos Chrysanthemi Indici resources, and explore new exploration for Chinese medicine to cure hypertension.

高血压是危害人类健康常见病，常伴心、脑、肾、眼等严重并发症。“过食肥甘醇酒”等不合理膳食，中医认为使机体“中满内热”致生热毒；会引发肠道菌群失调和肠屏障功能受损，导致全身轻度慢性炎症，继而血管功能和结构受损、胰岛素抵抗、RAAS系统异常激活及水钠滞留等，最终形成代谢性高血压，已成为高血压病主体。单降压化药疗效不理想，且需终身用药。野菊花具有清热解毒功能和降压疗效，前期研究明确了野菊花黄酮成分最优配比，对炎症因子有调节作用，能抑制LPS等诱导的血管细胞炎症。本课题在课题组长期中药抗高血压研究的基础上，以代谢性高血压模型为主，研究野菊花黄酮对肠道菌群、肠屏障功能、体内LPS水平及激活的相关信号通路、炎症反应等影响，并观察其对血管功能、胰岛素抵抗、RAAS系统、SNS系统等影响。阐述野菊花黄酮抗高血压的机制及特色，为降压新药研发、野菊花资源充分利用奠定基础，并为中药治愈高血压开展新的探索。

高血压是危害人类健康常见病，长期“过食肥甘醇酒”等不合理膳食，会使机体“中满内热”致生热毒，诱发“肠源性LPS/TLR4炎症途径”的激活，继而引起血管内皮功能受损、RAAS系统过度激活等而形成代谢性高血压。野菊花具有“清热解毒”之功，前期研究已发现野菊花黄酮具有降血压作用，但其防治代谢性高血压的药效及优势特色有待明确，且其作用机制尚未阐明。.本研究创新性采用拟人“过食肥甘醇酒”致代谢性高血压动物模型，明确了野菊花黄酮抗代谢性高血压的药效，并阐述了其在降血压的同时还兼具调节糖脂代谢、保护肝肾等优势特色，体现了其降压统筹兼顾的特点。并着重基于肠源性LPS/TLR4炎症途径，从肠源性LPS生成、移位及其介导的TLR4通路等多个关键环节，结合体内动物与体外细胞水平，首次揭示了野菊花黄酮抑制肠源性LPS/TLR4炎症途径抗代谢性高血压的创新机制。在此基础上进一步拓展了野菊花黄酮的成药性研究，率先研发了高效特色抗高血压创新中药—复方野菊花黄酮颗粒。本项目阐释了野菊花“清热解毒”的现代科学内涵，为中药防治高血压的优势提供科学依据，为野菊花防治高血压的应用开发及资源充分利用奠定基础。发表学术论文10篇，其中SCI论文7篇（JCR 1区3篇）；副主编学术专著1部；获浙江省科技进步二等奖1项；授权国家发明专利1项；研发创新中药1个；完成了项目的全部研究内容及任务指标。