Sphk1/S1P/S1PR介导“骨-血管轴”对话及田黄片“异病同治”科学内涵研究

钙在骨质的丢失和在血管的沉积这两种相反的病理状态称为“钙化悖论”，导致临床上骨质疏松症与动脉硬化常并发或伴发，但其具体病理机制尚不清楚，临床也无针对性药物，成为研究热点和难点。项目组前期在国家和省基金资助下，发现Sphk1/S1P介导二者的形成，中药复方田黄片具有双重干预作用。那么Sphk1/S1P是否是“钙化悖论”的关键机制和靶点？其上下游具体如何发挥作用？这是否是田黄片“异病同治”的科学内涵？据此，本项目拟构建转基因模式动物sphk1-/-/ApoE-/-小鼠加去势诱导具备“钙化悖论”特征动物模型，血管内皮细胞和破骨细胞共培养体系，SphK1siRNA和过表达技术等，揭示Sphk1/S1P/S1PR介导骨质疏松症与动脉粥样硬化“骨-血管轴”对话机制及田黄片“异病同治”科学内涵。既为疾病防治提供可能的新靶点和新思路，也为临床提供有效候选药物，具重要理论意义和实用价值。

The two opposite pathological states of calcium loss in bone and deposition in blood vessels are called “calcification paradox”,which leads to osteoporosis and arteriosclerosis often complicate or accompany in clinic. but the pathological mechanism is not clear, and there is no targeted drug, which has become a research hotspot and difficulty. Under the support of the National Natural Science Foundation and Guang Dong Provincial Natural Science Foundation projects, we found that the formation of both was mediated by SphK1/S1P, and THF, a traditional Chinese medicine, has the effect of “homotherapy for heteropathy”. Why can THF for the different diseases? What role does the Sphk1/S1P pathway play in the “calcification paradox”? On the basis, the project intends to explore the mechanism of “Bone-vascular axis ”cross talk between osteoporosis and atherosclerosis based on SphK1/S1P and the “homotherapy for heteropathy ”of THF by using Sphk1-/-/and ApoE-/- mice with OVX, HUVEC and Osteoclasts cell co-culture, Sphk1 siRNA and other technologie. It not only provides new targets and ideas for disease treatment, but also provides effective candidates drug for clinical application. It has important theoretical significance and practical value.