基于TGF-β/Wnt-β-Catenin/PPARs信号轴研究桑杞清眩颗粒对SHR心、肾及大血管损伤的作用机制

桑杞清眩颗粒是本课题组近二十年临床应用凝聚而成的中药制剂，前期临床和基础研究证实该药有降压、抗心室重构作用，其机制与TGFβ及PPARs炎症上游因子相关，但具体靶点和网络机制尚未明确。TGFβ/Smads、Wnt-β-catenin、PPARs信号通路介导的炎症反应，是目前高血压靶器官损害的研究热点。综上我们提出科学假说：桑杞清眩颗粒通过调节TGFβ/Wnt-β-Catenin/PPARs信号轴的炎症介导作用，发挥“益肾健脾，化痰消瘀”之功，减轻高血压靶器官损害。拟用SHR模型，检测中药干预后心、肾、大血管结构及病理变化，系统验证其靶器官保护作用；通过在体实验（信号轴相关因子表达）和体外实验（药物超微颗粒、shRNA慢病毒与含药血清）从器官-组织-细胞-分子-基因水平逐层探讨该中药调控TGFβ/Wnt-β-Catenin/PPARs信号轴的精确靶点，为中药治疗高血压靶器官损害提供客观依据。

Sangqiqingxuan Granule (SQQX) is a herbal preparation extracted from our clinical practice in the past two decades. Our previous study has proved that SQQX can decrease blood pressure and prevent ventricular remodeling. Meanwhile, these effects are proved closely related to the up-stream inflammatory factors of Transformin growth factor beta(TGFβ) and Peroxisome proliferator receptors(PPARs) signaling ways, yet the accurate taget site and signaling network are still unclear. The inflammatory reaction induced by TGFβ,Wnt-βcatennin and PPARs pathways is a hot spot in the pathogenesis of hypertensive target organ damage. Based on former researches, we propose a hypnosis that SQQX can alleviate the inflammatory reaction induced by the TGFβ/Wnt-β catenin/PPARs Axis to resolve phlegm and activate the blood circulation, tonifying kidney and spleen to attenuate hypertensive target organ damage. We plan to evaluate the heart, kidney and large arteries’ structure viariation in spontaneous hypertension rats (SHRs) after SQQX intervention, in the meantime, systematically validate the hypertensive target organ damage protecting effect of SQQX. Via in vivo(molecular factors expression in signaling axis) and in vitro(micro granules, shRNA lentivirus and drug serum) experiments, we aim to figure out the molecular mechanisms and precise target sites of the target organ protecting function of SQQX through adjusting the TGFβ/Wnt-β catenin/PPARs Axis on a organ-tissue-cell-molecule-gene level so that we can help provide experimental data and evidence for further adopting Traditional Chinese Medicine(TCM) to relieve hypertensive target organ damage.