糖皮质激素性骨质疏松（GIO）是临床致残性骨代谢疾病，发生机制尚未阐明。目前，氧化应激被认为参与GIO发病。我们发现，GIO大鼠骨组织微循环障碍，与TXNIP介导的线粒体应激有关，同时丹参的水溶性成分丹参素是其防治GIO的物质基础。新近报道，骨微血管生成调控骨形成。结合GIO血瘀证的中医病机，我们推测：TXNIP介导的线粒体应激负性调控骨微血管生成，造成血瘀证微循环障碍，可能是GIO发病的新机制。本项目拟复制GIO大鼠模型，动态观察线粒体应激和微血管形成与骨形成的变化规律，分析TXNIP介导的线粒体应激对血管内皮祖细胞的影响，在体外应用TXNIP过表达和RNA干扰技术，阐明TXNIP调控VEGF/Wnt通路对血管形成和骨形成的作用，从整体动物、细胞和线粒体水平揭示线粒体应激引起血瘀证微循环障碍在GIO发病中的作用及丹参素的干预机制，为活血化瘀中药防治GIO提供新的理论依据。

Glucocorticoid-induced osteoporosis (GIO) is one of disabling bone metabolic diseases clinically, and the pathogenesis has not been elucidated. Currently, oxidative stress is known as involvement in the pathogenesis of GIO. Previously evidence in our team revealed that skeletal microcirculatory abnormalities associated with mitochondrial stress mediated by TXNIP in GIO rat. We also found that tanshinol considered as active component of water-soluble fraction isolated from Danshen is the material base for the treatment of GIO. Recent publishes revealed that microvascular angiogenesis in skeletal tissue regulates bone formation. Considering the pathogenesis of traditional Chinese Medicine (TCM) associating with in blood stasis of GIO, we hypothesis that mitochondrial stress mediated by TXNIP might down-regulate bony microvascular angiogenesis, contributing to skeletal microcirculatory abnormalities of blood stasis in TCM. This may be potential pathogenesis of GIO. This research aims to observe the changes in mitochondrial stress, microvascular angiogenesis and bone formation, and to confirm inhibitory effect of mitochondrial stress mediated by TXNIP on endothelial progenitor cells(EPCs) in GIO model of rats. The research also aims to elucidate the influence of VEGF/Wnt pathway regulated by TXNIP on angiogenesis and bone formation in vitro using overexpression and siRNA of TXNIP technology. Then the research plans to reveal the inhibitory effect of mitochondrial stress on skeletal microcirculatory abnormalities of blood stasis in the pathology of GIO and the underlying mechanism of tanshinol. The study may be expanded to provide a new theory of agents for prmoting blood circulation and removing blood stasis to treat GIO.