天麻素调控RAS/CerS6/eNOS通路改善血压和血管内皮功能的机制研究

高血压是全球死亡的首要危险因素，中医药作为中华民族传统文化的瑰宝，可用于治疗高血压并减少各种不良反应的发生。我们前期研究发现，经典方剂天麻钩藤颗粒可显著降低24小时血压，而其作用机制尚不清楚。天麻钩藤颗粒的核心物质天麻素可以抑制RAS活性，而RAS和神经酰胺通路密切相关。我们前期研究表明，高血压模型鼠肾脏神经酰胺合成酶CerS6的转录和表达水平显著低于正常对照组。鉴于上述理论基础和研究结果，我们提出假设： RAS/CerS6/eNOS可能是介导天麻素参与血压和血管内皮功能调节的关键通路。本研究拟利用自发性高血压大鼠和Ang II诱导的高血压小鼠模型，探讨 1）高血压模型鼠RAS/CerS6/eNOS通路的变化；2）天麻素对高血压模型鼠RAS/CerS6/eNOS通路的作用；3）过表达或敲除CerS6基因对天麻素调节血压和血管内皮功能的影响。本研究有助于揭示中医药治疗高血压的新机制。

Hypertension is the primary risk factor for global mortality. Traditional Chinese medicine (TCM), as a treasure of Chinese traditional culture, can be used to treat hypertension and reduce the occurrence of various adverse reactions. Our previous study found that gastrodia-uncaria granules, a classic Chinese prescription, can significantly reduce 24-hour blood pressure, but the mechanism remains unclear. Gastrodin, the core substance of gastrodia-uncaria granules, can inhibit the activity of RAS, which is closely related to ceramide pathway. Previous studies showed that the transcription and expression levels of ceramide synthase 6 (CerS6) in hypertensive rats renal were significantly lower than those in normal control group. In view of the above theoretical basis and results, we hypothesize that RAS/CerS6/eNOS may be a key pathway that mediates gastrodin's involvement in the regulation of blood pressure and vascular endothelial function. In this study, we used spontaneous hypertensive rats and Ang II-induced hypertensive mice to investigate 1) the role of RAS/CerS6/eNOS pathway in hypertension. 2) The effect of gastrodin on RAS/CerS6/eNOS pathway in hypertensive model; 3) Effects of overexpression or knockout of CerS6 gene on the regulation of blood pressure and vascular endothelial function by gastrodin. This study is helpful to reveal the new mechanism of TCM treatment of hypertension.