基于代谢组学的桃红四物汤调节骨代谢的分子机制及物质基础研究

Bones strong depends on Qi and blood maintenance which is the key to maintain normal form and function of bones. However, blood stasis, main and collateral channels blocked and bones loss of nutrition could lead to osteoporosis. On the basis of preliminary study, guided by the Chinese medicine theory of promoting blood circulation and removing blood stasis in treatment of osteoporosis, the project with classical Taohong Siwu Decoction as the research object, the molecular mechanisms and bioactive components of Taohong Siwu Decoction on bone metabolism in whole animal and cellular molecular level will be studied using the of metabolomics and gene chip advanced methods and technologies. The following works will be carried out: (1) Based on the metabolomics methods and techniques, the intervention effects of Taohong Siwu Decoction on metabolic phenotype, osteoporosis biomarkers and metabolic pathway will be revealed. (2) The interaction effects of Taohong Siwu Decoction on the known targets in osteoblasts will be studied. The potential targets and signal pathway will be discovered by gene chip methods and techniques. (3) The key biomarkers (targets) in gene and protein level will be comfirmed. The interaction effects of Taohong Siwu Decoction and its components on the key biomarkers (targets) will be studied. The final objects of these studies are to systematically clarify the molecular mechanisms and the bioactive components of Taohong Siwu Decoction on bone metabolism, to provide the scientific basis for the Chinese medicine clinical application of promoting blood circulation and removing blood stasis in treatment of osteoporosis, and to provide reference of the discovery and development of new drugs from classical prescription.

骨骼强健依赖后天气血充养，气血对骨骼的滋养是骨骼维持正常形态和功能的关键，而一旦瘀血阻滞，脉络不通，骨失所养，必发为“骨痿”。鉴于此，本项目基于前期研究积累，从瘀论治骨质疏松症的中医思想指导下，以经典活血化瘀方剂桃红四物汤为研究对象，在整体动物和细胞分子水平系统地揭示桃红四物汤调节骨代谢的分子机制及物质基础，拟开展工作：（1）基于代谢组学的方法，明晰桃红四物汤对去卵巢大鼠骨质疏松症的代谢表型、生物标志物及代谢通路的干预作用。（2）选择已知作用靶点，在基因和蛋白水平考察桃红四物汤对成骨细胞分化和功能的影响；同时采用基因芯片技术，发掘潜在的作用靶点和信号通路。（3）从基因和蛋白水平进一步确认潜在的关键生物标志物（靶点），评价桃红四物汤及各化学组分的干预作用。最终阐释桃红四物汤调节骨代谢的分子机制及物质基础，为中医临床运用活血化瘀药治疗骨质疏松症提供科学依据，为从经典方剂中发现和创制新药提供参考

骨质疏松症严重威胁老年人口的健康。骨骼强健依赖后天气血充养，气血对骨骼的滋养是骨骼维持正常形态和功能的关键，而一旦瘀血阻滞，脉络不通，骨失所养，必发为“骨痿”。鉴于此，本项目在瘀论治骨质疏松症中医思想指导下，以中医临床治疗骨质疏松症常用有效活血化瘀方桃红四物汤为研究对象，在整体动物和细胞分子水平深入系统地揭示桃红四物汤治及其主要成分治疗骨质疏松的作用机制，以期阐释血瘀在骨质疏松症发病中的机理，促进活血化瘀法治疗骨质疏松症在临床的运用，提供中医治疗骨质疏松症新的方向，为研制与开发新型药物奠定基础。