高血压是最常见的心血管疾病，其发病机制未明。我们证实，肠道菌群紊乱参与高血压病的发生发展（Microbiome,2017）。前期研究发现，将高血压患者的优势菌K.pneumoniae（K.pn）移植给无菌小鼠（GF），使其血压升高，推测K.pn是导致高血压的致病菌，但作用机制尚不明确。本研究将通过GF移植模型明确K.pn促进血压升高的作用；对模型小鼠血清和粪便进行质谱分析，解析K.pn的代谢产物短链脂肪酸（SCFA），检测Olfr78/Gpr41受体的表达水平和下游MAPK、RAS、Egr-1信号，通过干预受体表达，阐明K.pn调控SCFA-Olfr78/Gpr41，RAS/MAPK/Egr-1通路进而引起血压升高；对K.pn进行基因信息组学分析找到关键代谢酶基因，通过敲除该基因，明确其对血压的调节作用被阻断，揭示K.pn导致血压升高的遗传学机制，为高血压临床转化研究提供新的治疗靶点。

Hypertension is a most prevalent cardiovascular diseases, and the pathogenesis is unclear. We have proved that disordered gut microbial structure and function participate in the development of hypertension (Microbiome,2017). Based on our previous findings of germ-free mice receiving K.pn transplantation, which is dominant in hypertensive patients, showed higher blood pressure, we speculated that K.pn might be the pathogenic bacterium leading to hypertension. However, the mechanisms remain unclear. In this project, we plan to confirm the effect of K.pn on blood pressure elevation, by inoculate transplantation to germ-free mice. Next, we plan to analyze the serum and fecal metabolism changes of recipient mice by LC-MS/MS, identify the Short-chain fatty acids (SCFA) produced by K.pn, determine the expression of Olfr78/Gpr41 receptor and MAPK、RAS、Egr-1 signaling, and illuminate K.pn contribute to hypertension through SCFA-Olfr78/Gpr41, RAS/MAPK/Egr-1 pathway. Last, we plan to find the key metabolic enzymes/gene in K.pn for SCFA producing, observe whether the effect of K.pn would be blocked by interferencing the enzymes/gene, reveal the genetic mechanism by which K.pn contribute to elevated blood pressure, and offer a novel therapeutic target of hypertension for clinical translational research.