基于H型血管-骨形成偶联研究“过咸伤骨”的分子机制及补肾活血中药复方的干预

“过咸伤骨”是中医理论中五味太过伤及脏腑的重要内容之一，现代研究发现高盐摄入可促进骨量丢失，但机制尚不十分清楚。H型血管-骨形成偶联的发现为骨代谢的研究提供了较好的切入点。我们根据前期研究和预实验结果提出了高盐摄入可能通过H型血管-骨形成偶联影响骨代谢的假说，研究应用免疫组化、免疫荧光LSCM、细胞共育、含药血清、基因阻遏等技术，研究①高盐摄入后正常大鼠和去卵巢大鼠骨组织H型血管的形成、分布及与骨代谢的关系；②高盐状态对体外培养的骨髓血管内皮祖细胞向H型血管内皮细胞分化的影响；③并观察Dll4-Notch信号和Hif-1α在其中的作用及补肾活血中药复方的干预，评价相关性。目的意义：①阐释中医脏腑理论五味之“咸”与五脏之“肾”、奇恒之腑之“骨、脉”联系的现代科学内涵；②对于明确高盐摄入对骨代谢影响的病理生理学机制及饮食方式防治骨质疏松方面有重要指导作用；③阐释中药复方的多靶点网络药理学机制。

“Too salty to hurt the bone” is one of the important contents of too heavy taste hurt viscera in Traditional Chinese Medicine (TCM) theory, and modern medical research has also found that high salt intake can accelerate bone loss, but the mechanism is not clear completely ...The discovery of H-type vessel-bone coupling provides a good research point for the study of bone metabolism. Based on the results of previous studies and preliminary experimental, we propose a hypothesis that high salt intake may affect bone metabolism through H-type vessel -bone coupling...In this study, we will use immunohistochemistry, laser scanning confocal microscopy, cell co-culture, drug-containing serum, gene repression and other techniques to study: Firstly, the formation and distribution of H-type vessels in bone tissue of normal rats and ovariectomized rats after high salt intake and the relationship with bone metabolism; Secondly, the effect of high salt on the differentiation of bone marrow endothelial progenitor cells to H-type endothelial cells in vitro; Thirdly, the role of Dll4-Notch signal and Hif-1alpha and the intervention of a compound Chinese medicine for reinforcing kidney and activating blood circulation in the above conditions. ..To the end of the study，we will get a new scientific interpretation of the TCM theory of the relationship between Salt and Kidney, Bone and Vessel, which is important for the understanding of pathophysiologic mechanism of high salt affecting bone metabolism and the prevention and treatment of osteoporosis under the guidance of TCM theory; And we will also get the overall role of a compound Chinese medicine for reinforcing kidney and activating blood circulation treating osteoporosis through regulating H-type vessel -bone coupling.