芪参方肠道滞留成分通过调节短链脂肪酸Olfr78 /Gpr41肾脏-血管双感受器维系宿主血压平衡的作用机制

高血压为一种常见慢性心血管疾病，致病机制包含遗传、环境等多重因素，至今仍有待深入探究。最新研究揭示了肾脏和血管壁中一对短链脂肪酸感受器Olfr78/Gpr41与血压调节的关系。中医药以“补虚泻实，适其阴阳” 为原则治疗高血压病具有良好的临床疗效。因此我们提出“益气活血复方芪参方中肠道滞留成分通过菌群代谢产物协调肠、肾、血管Olfr78/Gpr41表达和功能，维系血压平衡”这一科学假说。基于本团队前期对“活血”中药活性成分的坚实研究基础，本课题拟以肾性和血管性高血压大鼠为模型，探讨芪参方中肠道滞留的“益气”活性成分与肠道短链脂肪酸的相互作用，在整体动物、肠/肾/血管靶器官和G蛋白偶联受体分子信号通路三个水平系统探究其对Olfr78和Gpr41血压感受器受体的差异调节，揭示 “益气”功能的血管生物学内涵和“益气”活性成分通过肠道菌群代谢产物差别影响肾性和血管性高血压大鼠血压平衡的作用机制。

As a common chronic cardiovascular disease, the pathogenesis of hypertension involves complex factors including gene and environment, which remain to be fully explored. The latest research reveals a new mechanism of homeostasis of host blood pressure that is regulated by a pair of SCFA-sensing blood pressure receptors Olfr78 and/Gpr41 in the renal and vascular walls, regulated by the intestinal microflora metabolites. Chinese medicine has a rich clinical basis and proven effect on the treatment of hypertension with the principle of "reinforcing deficiency and reducing the reality and adapting Yin and Yang". Therefore, we put forward the scientific hypothesis of "intestinal retention components of the Qi-benefiting/Blood-activating compound Qishen formula maintain blood pressure balance through intestinal microflora metabolites, which coordinate the expression and function of SCFA-sensing Olfr78/Gpr41 dual receptors in intestine, kidney and blood vessels. Based on a solid research foundation of this team on the "blood-activating components in Chinese medicine, this project aims to utilize rat renal (RHR) and vascular (SHRsp) hypertension models to investigate the interactions of “Qi-benefiting” intestinal retention components of Qishen formula with intestinal SCFA at the levels of the whole animal, intestinal / kidney / vascular targeting organs and molecular G-protein coupled receptor signaling system, exploring their differential regulation on kidney Olfr78 and vascular wall Gpr41 dual blood pressure receptors. The goal of the research is to reveal the vascular biology connotation of “Qi”, and the mechanism of “Qi-benefiting” active ingredients in the maintenance of blood pressure homeostasis through the intestinal microflora metabolites in renovascular hypertension.