三七总皂苷抑制破骨细胞外泌体miR-214负向调节ephrinA2-EphA2通路促进成骨细胞生成在激素性股骨头坏死中的机制研究

前期研究发现，SONFH中ephrinA2-EphA2信号通路处于激活状态，使破骨细胞增殖；三七总皂苷（PNS）具有活血化瘀的作用，可以负向调节ephrinA2-EphA2信号通路抑制破骨细胞增殖并促进成骨细胞生成，但具体分子机制不明确。最近研究发现破骨细胞外泌体miR-214可以与成骨细胞结合，并激活ephrinA2-EphA2信号通路抑制成骨细胞的生成；据此提出假说：PNS可抑制破骨细胞外泌体miR-214表达，负向调节ephrinA2-EphA2信号通路从而促进成骨细胞生成，起到修复SONFH的作用。为验证假说，我们建立SONFH小鼠模型及提取破骨细胞外泌体miR-214作用于成骨细胞进行体内外实验，探讨PNS干预前后miR-214表达及ephrinA2-EphA2信号通路的动态变化，明确PNS在SONFH中的作用机制，为临床使用活血化瘀中药治疗SONFH 提供新靶标。

Pprevious studies found that the ephrinA2-EphA2 signaling pathway in SONFH was activated, leading to osteoclast proliferation.Total saponins of notoginseng (PNS) can activate blood circulation and reduce blood stasis, and negatively regulate the ephrinA2-EphA2 signaling pathway to inhibit osteoclast proliferation and promote osteoblast formation, but the specific molecular mechanism is unclear.Recent studies have shown that osteoclast exosome miR-214 can bind to osteoblasts and positively regulate the ephrinA2-EphA2 signaling pathway to inhibit the generation of osteoblasts. Therefore, proposed the hypothesis that PNS could inhibit the expression of osteoclast exosome miR-214 and negatively regulate the ephrinA2-EphA2 signaling pathway, thereby promoting the generation of osteoblasts and playing a role in repairing SONFH. In order to verify the hypothesis, we established a SONFH mouse model and extracted osteoclast exosome miR-214 to act on osteoblasts for in vivo and in vitro experiments, to explore the dynamic changes of miR-214 expression and ephrinA2-EphA2 signaling pathway before and after PNS intervention, and to clarify the mechanism of PNS in SONFH, so as to provide a new target for clinical application of traditional Chinese medicine for activating blood and removing stasis in SONFH.