干细胞介导的内源性修复是维持组织内环境稳定的天然保护机制之一，有证据显示退变髓核组织中存在间质干细胞，研究如何激活自身干细胞，从而启动内源性修复，将为椎间盘退变性疾病的生物学治疗提供新思路。文献报道髓核间质干细胞在低氧时可向髓核细胞分化，缺氧诱导因子（HIF）是低氧应答时恢复细胞内环境稳定的调节中心，可通过激活一系列靶基因发挥作用。我们前期研究发现HIF-1α通过上调葡萄糖转运蛋白1等因子延缓椎间盘退变。目前发现他汀类药物可诱导多种间质干细胞分化为目标细胞，而其对髓核间质干细胞的作用如何仍不清楚。由此，我们提出以下假设：辛伐他汀通过调控HIF-1α来调控髓核间质干细胞向髓核细胞分化的生物学行为等途径内源性修复重建退变椎间盘功能。为进一步证实此假说，本课题将从细胞及动物水平证实辛伐他汀通过调控HIF-1α表达逆转椎间盘退变进程。本研究以期深化对椎间盘退变内源性修复的理解，为其治疗开辟新思路

Stem cell-mediated endogenous repair is one of the natural protective mechanisms to maintain stable environment. The activation of stem cell existing in the degenerative nucleus pulposus to achieve endogenous repair will provide new ideas to biological therapy of degenerative disc disease. The nucleus pulposus-derived stem cell can differentiate into nucleus pulpous in hypoxia condition.Hypoxia-inducible factor (HIF) is the regulation center to restore the intracellular homeostasis by activating a series of target genes faced with.hypoxia.HIF-1α can retard disc degeneration through upregulation of glucose transporter 1 and other factors found in our previous study. The evidence confirmed that statins can induce a variety of mesenchymal stem cells differentiate into target cells, however the effect of statins to the nucleus pulposus-derived mesenchymal stem cell remains unclear.Thus, we hypothesize HIF-1α mediated simvastatin regulates biological behavior of nucleus pulposus-derived mesenchymal stem cell to endogenous repair and reconstruct degenerative intervertebral disc. To further verify this hypothesis, the study will test whether simvastatin can reverse the process of disc degenaration in the cell and anmial levels along with the change of HIF-1α expression. The study is to deepen the understanding of the mechanisms of endogenous repair of degenerative disc and develop new ideas for treatment