乳铁蛋白通过调节肠道菌群防治高血压

乳铁蛋白（Lf）及其活性肽具有抑制血管紧张素转换酶（ACE）活性的作用，从而达到降压效果，但是体外具有ACE抑制活性的肽并非一定降低实验动物的血压，人群研究和动物实验的结论也不一致。因此，Lf调节血压可能还存在其他路径。最近的研究证实肠道菌群紊乱与高血压的发生发展密切相关，而且Lf能够调节肠道菌群，因此申请人提出“Lf通过调节肠道菌群防治高血压”的假说。本研究通过自发性高血压大鼠（SHR）和轻度高血压患者，动态观察Lf干预对血压、血管内皮功能与肠道菌群及其代谢产物短链脂肪酸、氧化三甲胺的影响。在动物实验部分，采用Lf干预内源性肠道菌群清除的SHR大鼠、以及移植Lf干预的SHR大鼠的肠道菌群至WKY大鼠（血压正常的对照鼠）等手段观察肠道菌群、肠道菌群代谢产物在Lf调节血压中的“净”效应。本研究以肠道菌群为切入点研究膳食营养素预防高血压，为高血压病综合防治提供了新的科学证据。

Lactoferrin (Lf) and Lf-derived active peptides had inhibitory effect on angiotensin converting enzyme (ACE), lowing blood pressure (BP). However, not all ACE inhibitory peptides in vitro can observe the decrease of BP of experimental animals, and the results between human trials and animal experiments were conflicting. Thus, other mechanism plays the role in the BP regulation by Lf supplementation. Recent studies demonstrated that gut dysbiosis is related to hypertensive incidence and development and Lf has role on regulating gut microbiota. Therefore, we put forward a hypothesis that Lf regulates BP through gut microbiota. In this application, we investigate the effects of Lf intervention on the BP values, endothelial dysfunction, gut microbiota and its metabolites such as short chain fatty acids and trimethylamine oxide in spontaneously hypertensive rats (SHR) and mildly hypertensive patients. In animal study, “net” effect of Lf on BP regulation is observed by the Lf intervention on SHR rats previously treated with antibiotics to reduce the native microbiota, and gut microbiota transplant from Lf treated SHR to Wistar Kyoto (WKY) rats with normal blood pressure. In this application, we investigate the BP prevention by nutrients through gut microbiota and provide the new scientific evidence on comprehensive prevention and treatment of hypertension.