在过去十几年里，因下腰痛而就诊的病人数量并未下降，下腰痛仍无可靠的治疗措施，其中腰椎间盘退变是下腰痛发生的最主要原因。腰椎软骨终板（CEP）退变和异常钙化在椎间盘退变和下腰痛中扮演了关键角色，但其机理仍旧不明。我们前期研究发现Indian Hedgehog（Ihh）在退变CEP中的表达增高，升高的Ihh可以促进CEP基质的降解，而在体外研究发现阻断Ihh信号通路能够抑制人CEP的降解。其他研究小组运用基因敲除小鼠证实激活Ihh信号通路能够促进钙化。目前，国内外其他实验室尚无关于Ihh在CEP中作用和机制的报道。为了进一步深入研究Ihh在腰椎CEP退变和异常钙化中的作用和机制，本课题组拟在加强体外研究的基础上，结合Ihh条件性基因敲除小鼠和LNP-RNAi基因敲除技术，运用活体荧光分子断层扫描及其他常规手段，探求Ihh在CEP病变中的作用和可能机制，为未来Ihh的靶向治疗提供可行方案。

In the past decade, the number of low back pain outpatients does not decrease, because the mechanism of LBP is still unclear and there is no reliable way to cure the disease. Research shows that lumbar intervertebral disc degeneration is the most common reason for low back pain, whereas the degeneration and abnormal calcification of lumbar cartilaginous endplates (CEP) play a critical role in intervertebral disc degeneration and low back pain. Previously, our studies found that there was a significant increase of Indian Hedgehog (Ihh) mRNA in human degenerative CEP chondrocytes. Furthermore, Ihh could promote the degradation of the CEP extracellular matrix in vitro and the progression of CEP degeneration could be inhibited by blocking the Ihh signaling pathway. Studies by other groups demonstrate that activation of Ihh signaling pathway can promote tissue calcification in vivo. As far as we know, we are the first group focusing eyes on the effect of Ihh on the CEP. Base on these findings, we propose to investigate the role of Ihh in CEP degeneration and abnormal calcification by using the aggrecan specific Ihh conditional knockout mice, as well as lipid nano-particle (LNP) RNAi technology to interfere Ihh expression in the rats CEP chonchocytes. Our study may probably provide a theoretical foundation for targeted biological therapy for the treatment of lumbar CEP disease.