血管平滑肌细胞(vascular smooth muscle cell, VSMC)成骨样转化是慢性肾脏病(chronic kidney disease, CKD)发生血管钙化的中心环节，而Wnt/b-catenin信号在VSMC成骨样转化和钙化程序中发挥重要的调控作用。白藜芦醇对血管钙化具有潜在的干预效应，而Wnt/b-catenin信号有可能是其关键的作用靶点。由此提出科学假说：白藜芦醇可通过调控Wnt/b-catenin信号活化状态，干预CKD环境中VSMC成骨样转化与血管钙化。本项目拟从体外、离体和体内三个层面，通过研究白藜芦醇对CKD环境中VSMC成骨样转化和钙化程序的影响，揭示白藜芦醇对CKD血管钙化的防治效应；通过研究白藜芦醇对VSMC内Wnt/b-catenin信号活化状态的影响，阐明其作用的分子机制，为其临床应用及探索防治CKD血管钙化的新措施提供有益思路。

Vascular calcification is highly prevalent in patients with chronic kidney disease (CKD) and contributes to increased risk of cardiovascular disease and mortality. Accumulated evidences suggested that vascular smooth muscle cells (VSMCs) to osteoblast-like cells transdifferentiation (VOT) is a crucial mechanism in promoting vascular calcification in CKD patients. In addition, Wnt/b-catenin signaling has been shown to play an essential role in the regulation of VOT in a high-phosphate environment which is a common phenomenon in CKD patients. Recently, the potential effect of resveratrol on interfering with VOT and vascular calcification has emerged while Wnt/b-catenin signaling has been presented to be a probable target of resveratrol in several other types of cells. Therefore, the hypothesis that through manipulating Wnt/b-catenin signaling, resveratrol plays a critical role in inhibiting the process of VOT and vascular calcification in CKD is put forword..This research project will be set up as follows. First of all, in vitro, ex vivo and in vivo models of chronic renal failure, a severe stage of CKD, followed by vascular calcification will be established, respectively. Then the effects of resveratrol on each key step during the process of VOT will be studied one by one and the pathological changes in the aorta tissue by resveratrol will be analysed in detail. Furthermore, the capacity of resveratrol in regulating the activity of Wnt/b-catenin signaling in VSMCs will be assayed. Finally, by manipulating the activity status of Wnt/b-catenin signaling either by ectopic expression of specific genes of the signaling pathway or by applying specific recombination proteins of it in vitro, the influence of resveratrol on VOT and vascular calcification will be detacted..The results presented in the studies of this project will demonstrate that through targeting Wnt/b-catenin signaling, which in turn impeding VOT, resveratrol possesses a potent effect on retarding vascular calcification in CKD.