申请者在青年项目资助下证实：补肾古方青娥丸加味（QEF）可有效防治早期股骨头缺血性坏死 (INFH) 的进展，可能通过上调骨组织局部1,25-(OH)2D3及VDR mRNA的表达有关，我们的研究进一步证实1,25-(OH)2D3可通过负性调节局部肾素-血管紧张素系统（RAS）部分组分进而调节骨转换水平。因此我们推测QEF防治早期INFH的深入机制可能与RAS系统相关。我们进而查阅文献发现RAS具有参与调控局部微循环及炎症反应，介导氧化应激及调节骨转换的作用，使得我们更有理由推测RAS系统在INFH的发生发展中起关键调控作用。因此本项目以骨组织局部RAS双轴[ACE/AngII/AT1R轴和ACE2/Ang(1-7)/Mas轴]信号通路为核心，综合血管新生及骨修复两层面，探讨此信号通路在INFH中的生物学效应及QEF的作用靶点，为进一步掌握INFH的病理机制及创新中药治疗提供实验基础。

Our applicants supported by the Youth Project of NSFC confirmed that QEF could effectively prevent and treat the progress of early ischemic necrosis of the femoral head (INFH), possibly by up-regulating the expression of 1,25-(OH)2D3 and VDR mRNA in bone tissue. Our study furtherly confirmed that 1,25-(OH)2D3 could be regulated by negatively regulating some components of the local renin-angiotensin system (RAS), then regulating the bone turnover level. Therefore, we speculate that the mechanism of QEF in preventing and treating early INFH may be related to RAS system. We further consulted the literature and found that RAS plays a key role in regulating local microcirculation and inflammation, mediating oxidative stress and regulating bone turnover, which makes it more reasonable to speculate that RAS system plays a key role in the occurrence and development of INFH. Therefore, this project takes the local RAS biaxial signal pathway [ACE/AngII/AT1R axis and ACE 2/Ang(1-7)/Mas axis] of bone tissue as the core, combines the two levels of angiogenesis and bone repair, and explores the biological effects of this signal pathway in INFH and the role of QEF targets, so as to provide experimental basis for further understanding the pathological mechanism of INFH and innovating the mechanism of traditional Chinese medicine treatment.