椎间盘退变（IVDD）机制不明，有报道IVDD状态下髓核细胞糖代谢异常，导致乳酸产物升高。课题组前期发现长时间乳酸作用抑制髓核细胞功能（J Orthop Res，2014），但短时高浓度乳酸作用可促进低营养状态下髓核细胞的存活，并上调功能蛋白表达。本项目拟进一步研究乳酸对髓核细胞的生理病理作用及其表观遗传学调控机制。研究首先采用髓核细胞培养模型，分析乳酸对髓核细胞产生生理、病理作用相应的浓度、时间，并筛选相关代谢性表观基因改变；然后通过敲减乳酸引起髓核细胞改变的主要表观基因，研究乳酸作用的表观遗传学机制；最后采用大鼠正常椎间盘和针刺IVDD模型，在体研究不同运动强度、时间产生的乳酸浓度，并以乳酸最佳作用浓度对应的运动方式应用于IVDD，获得合适的运动康复方案。本研究的发现将创新性地从代谢角度阐明髓核细胞功能调控的表观遗传机制，同时将为IVDD提供新知识和新康复方案。

The pathogenesis of intervertebral disc degeneration(IVDD) is not clear yet, there are reports of abberrant state of nucleus pulposus cell(NPC) glucose metabolism druing IVDD, which leads to increased lactate production. Our previous study have found that long-term treatment of lactate downregulates NPC function (J Orthop Res, 2014 ), but short-term and high concentration treatment has protective effect on NPC, suggesting effect of lactate on NPC varies by different modes of action. This project is a systemic and in-depth study of the effect of lactate on NPC function and its mechanism. In this study, using NPC cell culture model, the physiological and pathological concentration of lactate for NPC function and differentially expressed epigenetic genes will be screened. Then through knocking-down main NPC function related epigenetic genes, we will study the epigenetic mechanism of physiological and pathological effects of lactate on NPC. Finally, normal and acupuncture induced IVDD animal models will be applied to elucidate the relationship between exercise stimuli and physiological and pathological effect of lactate, we aim to develop new exercise rehabilitation program for IVDD. Findings of this study will be an innovative way to clarify the the molecular regulation mechanisms of NPC function from a metabolic point of view, and will provide new knowledge and new program for spinal rehabilitation.