基于整合素/细胞外基质探讨补阳还五汤苷类有效组分促进内皮祖细胞修复受损血管内皮作用的研究

Our previous studies showed that BYHWD could promote EPCs repairing damaged vascular endothelium，and the mechanism was about improving internal environment, accelerate EPCs homing and differentiation. But the material foundation of efficacy, impact target and material foundation of efficacy were unclear. Our recent researches discovered that the glycosides were the active principle of BYHWD, the literature reviews indicated the indicate of ECM and integrins was important channel to regulate EPCs homing, invasion and differentiation, thus, studying ECM and integrins as the target was of great scientific significance to definite effective substance and mechanism of action. In conclusion, we propose the hypothesis, based on the theoretical system of TM, employed experiments of in vivo and vitro, linked with EPCs homing, invasion and differentiation, targeted with ECM and integrins, through the lay of protein and signal path，to discuss the mechanism of the glycosides promote EPCs repairing damaged vascular endothelium, thereby, we could found the material foundation of efficacy, impact target and material foundation of efficacy, from which we could discovery the new way to prevent and treat cardiocerebral vascular diseases, and provide theoretical and experimental reference to accurate CM.

本课题组已有的研究表明BYHWD可促进EPCs修复损伤的血管内皮。其机制与改善内环境，促进EPCs归巢、分化有关。但该方的药效物质、作用靶点和机制还有待研究。我们已有的研究发现苷类组分是该方的有效组分，文献研究表明ECM和整合素相互作用是调节EPCs归巢、迁移和分化的重要途径，因此，以苷类组分调控整合素/ECM为新靶点开展研究，对于进一步明确药效物质和作用机制具有重要的科学意义。综上所述，我们提出如下研究思路：在中医活血化瘀理论指导下，采用体外和在体实验，从EPCs归巢、迁移、分化环节，以整合素ECM/为靶点，从ECM/整合素相关蛋白及其FAK/ERK信号通路层面，探讨BYHWD苷类组分调控EPCs修复受损血管内皮的机制，从而发现该方的药效物质基础、防治疾病的作用靶点和机制，为中医药防治心脑血管疾病提供新途径，为中医药精准医疗提供实验依据和参考。

本研究在中医活血化瘀理论指导下，采用体外和在体实验，从EPCs归巢、迁移、分化环节，以整合素ECM/为靶点，从ECM/整合素相关蛋白及其FAK/ERK信号通路层面，探讨BYHWD苷类组分调控EPCs修复受损血管内皮的机制，从而发现该方的药效物质基础、防治疾病的作用靶点和机制。.研究结果表明：在BYHWD苷类有效组分的提取研究中，验证了已有的三类苷成分：黄芪甲苷、苦杏仁苷、芍药苷对血管内皮的保护作用，并发现了新的苷类物质，其保护血管的作用较显著。体外研究表明，补阳还五汤能通过够改善衰老 EPCs 的增殖、迁移及成管能力，起到抗衰老的作用，苷类组分为该方主要药效物质，其作用机制可能与抑制 ITGβ3和 ITGβ6 介导的 FAK/ERK 信号通路有关。在体的初步实验也证明，苷类组分能促进EPCs归巢和修复损伤的血管内皮，苷类组分的作用优于原方，提示苷类组分为原方保护血管内皮的主要药效物质。