补肾活血胶囊调控Hedgehog信号通路治疗激素性股骨头坏死作用与关键机制研究

Steroid-induced avascular necrosis of femoral head (SANFH) is a common complication of steroid therapy, which seriously do harm to the health of patients. So it is a hot and difficult point to find effective drugs and methods. The preliminary research had shown that Bushen Huoxue Capsule was positively involved in the regulation of adipose metabolism and the regeneration of bone tissue, and had a significant effect in the treatment of SANFH. We have already confirmed that the imbalance between BMSCs adipose and osteoblasts differentiation is the important factor to cause adipose tissue deposit, elevate intraosseous pressure and accelerate osteonecrosis, and that the Hedgehog signaling pathway is a critical signaling pathway in this process. So we speculate that the Hedgehog signaling pathway plays an important role in the pathogenesis of SANFH, which may be the key target of invigorating the kidney and activating blood circulation. From molecular, cellular, and animal levels, we investigate the role of Hedgehog signaling pathway in the pathogenesis of SANFH and the target of Bushen Huoxue Capsule through in vitro and in vivo on the basis of the preliminary work, pre-experiment and recent advances in the study of bone metabolism. The expected results will explain the role of Hedgehog signaling pathway in regulating bone metabolism in the treatment of SANFH and the key underlying mechanism, and enrich the scientific connotation of TCM theory of “kidney governing the bones and engendering marrow”, and provide new targets and approaches for clinical treatment.

激素性股骨头坏死（SANFH）是激素治疗的常见并发症，严重危害患者健康，发掘有效治疗药物及方法是目前研究的热点与难点。前期研究证实补肾活血胶囊调节脂质代谢、促进骨组织修复，治疗SANFH取得显著疗效。骨髓基质干细胞(BMSCs)脂肪分化与成骨细胞分化的平衡失调导致脂肪堆积是造成骨内压升高、骨坏死的重要因素，Hedgehog信号通路是此过程关键信号通路，推测Hedgehog信号通路在SANFH发病中具有重要作用，可能是补肾活血法干预的关键靶点。本研究拟通过体内外实验，从分子、细胞及整体水平，探讨Hedgehog信号通路在SANFH发病中的作用及补肾活血胶囊干预的靶点。本课题将阐释补肾活血胶囊通过Hedgehog信号通路调节骨代谢治疗SANFH的作用与关键机制，从而丰富中医学“肾主骨生髓”理论科学内涵，为临床治疗提供新的靶点与途径。

激素性股骨头坏死（SONFH）是激素治疗的常见并发症，严重危害患者健康，发掘有效治疗药物及方法是目前研究的热点与难点。前期研究证实补肾活血胶囊调节脂质代谢、促进骨组织修复，治疗SONFH取得显著疗效。骨髓基质干细胞(BMSCs)脂肪分化与成骨细胞分化的平衡失调导致脂肪堆积是造成骨内压升高、骨坏死的重要因素，Hedgehog信号通路是此过程关键信号通路，推测Hedgehog信号通路在SONFH发病中具有重要作用，可能是补肾活血法干预的关键靶点。.借助Mimics软件CT三维重建能快速直观地评估股骨头坏死组织的体积及分布情况。基于网络药理学和生物信息学研究能在一定程度上阐明补肾活血胶囊治疗SONFH的作用机制，有助于后续分子机制实验设计的优化。通过对临床坏死的股骨头样本进行分析，初步了探究了不同病因导致的ONFH的初步机制。基于Hedgehog信号通路补肾活血胶囊能促进SONFH大鼠的骨修复及血管生成、抑制其脂肪形成。补肾活血胶囊含药血清能通过Hedgehog信号通路促进BMSCs成骨分化及成血管方向的分化、抑制其成脂分化。.本研究通过体内外实验，从分子、细胞及整体水平，探讨Hedgehog信号通路在SONFH发病中的作用及补肾活血胶囊干预的靶点。本项目阐释了补肾活血胶囊通过Hedgehog信号通路调节骨代谢治疗SONFH的作用与关键机制，从而丰富中医学“肾主骨生髓”理论科学内涵，为临床治疗提供新的靶点与途径。本研究上述成果对于SONFH机制的研究与阐释以及中医药防治本病的作用机理具有重大意义，有利于中医药干预在骨坏死领域的推广。