激素性股骨头坏死为进展性的难治性疾病，给患者带来极大的痛苦，已成为非创伤性股骨头坏死的主要原因，其发病机制尚未完全阐明，目前尚无一种理想的治疗方法。3,4-二羟基苯甲酸乙酯（Ethyl-3,4-dihydroxybenzoate ,EDHB)为一种小分子脯氨酸羟化酶抑制剂，可以在常氧状态下抑制HIF-1α降解，促进其下游涉及血管生成、细胞能量代谢等方面基因表达，产生成骨成血管作用。使用EDHB对骨髓间充质干细胞（BMMSCs）进行预处理，是一种简便的改善BMMSCs性能的方法,可以改善单纯BMMSCs移植成活率低、分泌生长因子少等缺点,亦可促进BMMSCs的增殖和成骨分化。本研究拟探讨EDHB预处理的BMMSCs移植对家兔激素性股骨头坏死的预防及保护效果，并进一步研究EDHB对BMMSCs增殖分化影响的分子机制，为临床预防、治疗股骨头坏死及其机制的阐明提供一种新方法。

Avascular necrosis of femoral head is a progressive and refractory disease which brings great suffering to patients. Steroid-induced avascular necrosis of the femoral head has become the main reason for non-traumatic osteonecrosis of the femoral head, and its pathogenesis has not been fully elucidated.So far ,there is no ideal therapeutic method. Ethyl-3,4-dihydroxybenzoate(EDHB) is one of prolyl hydroxylase inhibitors which can stabilize hypoxia-inducible factor-1α（HIF-1α） under normoxic conditions, and then promotes its downstream target genes involved in angiogenesis, energy metabolism which can promote neovascularization and new bone formation .Preconditioning BMMSCs by EDHB is a simple way to improve performances of BMMSCs. EDHB can improve survival after bone marrow mesenchymal stem cells are transplanted.It can also promote the secretion of growth factors.Besides,EDHB can promoto the proliferation and osteogenic differentiation of BMMSCs. This study is to investigate the preventive effect and the clinical efficacy of BMMSCs transplantion preconditioned by EDHB on steroid-induced avascular necrosis of the femoral head. Furthermore,the study also explores the molecular mechanism involved in the effect of EDHB on BMMSCs so as to provide a new method for clinical prevention and treatment of osteonecrosis of the femoral head.

激素性股骨头坏死为进展性的难治性疾病，给患者带来极大的痛苦，已成为非创伤性股骨头坏死的主要原因，其发病机制尚未完全阐明，目前尚无一种理想的治疗方法。3,4-二羟基苯甲酸乙酯（Ethyl-3,4-dihydroxybenzoate ,EDHB)为一种小分子脯氨酸羟化酶抑制剂，可以在常氧状态下抑制HIF-1α 降解，促进其下游涉及血管生成、细胞能量代谢等方面基因表达，产生成骨成血管作用。使用EDHB 对骨髓间充质干细胞（BMMSCs）进行预处理，是一种简便的改善BMMSCs 性能的方法,可以改善单纯BMMSCs 移植成活率低、分泌生长因子少等缺点,亦可促进BMMSCs 的增殖和成骨分化。同时低氧预处理可以逆转股骨头坏死骨髓间充质干细胞的损伤，增强其修复性能。本研究发现EDHB 及缺氧预处理的BMMSCs 移植通过成骨成血管及抗凋亡作用对家兔激素性股骨头坏死发挥预防及保护作用，并研究EDHB及缺氧预处理 对BMMSCs 增殖分化影响的分子机制，发现预处理可以修复骨坏死中骨髓间充质干细胞的损伤，促进其再生能力及治疗潜能。同时研究发现氯化锂可以通过激活β-catenin通路，促进成血管及平衡成骨/成脂分化，为临床预防、治疗股骨头坏死及其机制的阐明提供一种新方法。