血管钙化是导致慢性肾脏病（CKD）患者心血管事件及死亡的重要危险因素，其发病机制尚未明确，且缺乏有效的治疗手段。既往研究提示外泌体可在血管钙化发生中起信号传递作用。我们前期研究发现，高磷刺激下血管内皮细胞外泌体可能通过miR-29b促进血管平滑肌细胞衰老和钙化，CKD大鼠钙化血管β-catenin表达增高。故提出，CKD早期血管内皮细胞通过外泌体向血管平滑肌细胞传递miR-29b，激活β-catenin通路，启动CKD血管钙化。本研究基于GSK-3β基因定向敲除的CKD小鼠模型，采用miRNA转染，外泌体提取、鉴定、摄取分析、靶向运输等技术，拟阐明血管内皮细胞通过外泌体传递miR-29b诱导血管钙化的机制，验证miR-29b通过抑制GSK-3β激活β-catenin通路，进而探究外泌体靶向传递miR-29b抑制物干预CKD血管钙化的有效性，为CKD血管钙化的新药研发提供理论依据。

Vascular calcification is an important risk factor for cardiovascular events and mortality in chronic kidney disease (CKD) patients. The underlying mechanism for CKD associated vascular calcification (CKD-VC) remains to be elucidated, and there is no effective treatment yet. It is suggested that exosomes may play a signaling role in the development of vascular calcification. According to our previous researches, exosomes secreted by vascular endothelial cells stimulated by high phosphorus could promote the senescence and calcification of vascular smooth muscle cells (VSMCs) via miR-29b. We also confirmed the high expression of β-catenin in calcified aorta in CKD rats. Therefore, we propose that in the early stage of CKD, vascular endothelial cells transmit miR-29b to VSMC via exosomes, activate β-catenin pathway, and initiate the process of CKD-VC. Our project builds targeted GSK-3β knockout CKD mice models, and utilizes the techniques of miRNA transfection, exosome extraction, identification, uptake analysis, and targeted transport. This study aims to clarify the mechanism how vascular endothelial cells transmit miR-29b through exosomes to induce vascular calcification, verify that miR-29b activate β-catenin pathway via inhibiting GSK-3β, and explore the efficacy of VSMC-targeted transmission of miR-29b via exosomes in the treatment of CKD associated vascular calcification. Our study may provide theoretical basis for the development of new drugs for CKD associated vascular calcification.