中文摘要
清热燥湿中药化学成分结构差异较大,但临床改善脂质代谢异常作用类似,推测清热燥湿中药不同化学成分分别作用于脂质代谢网络关键靶点,通过多向调节方式形成类似的干预脂质代谢效果。本项目拟选取黄芩、黄连、黄柏、龙胆、苦参等五种临床常用调节脂质代谢异常清热燥湿中药,制备含药血清,对油酸诱导脂肪蓄积肝细胞模型给药,采用基因芯片和抗体芯片技术比较基因和蛋白的表达差异;采用网络药理学方法,建立多层次结构化网络分析方法,评价清热燥湿中药调节脂质代谢的整体影响以及靶点间相互作用关系,确定关键节点和功能模块;结合化学成分研究结果,采用分子对接和虚拟筛选方法,预测可能药效物质;开展体内、外活性验证,明确清热中药改善脂质代谢异常药效物质物质及作用机制,总结规律,以期从中药临床经验中发现改善脂质代谢异常新靶点,为指导中药临床合理用药及创新药物发现提供科学依据。
英文摘要
Although alleviates fever eliminating dampness Traditional Chinese Medicines contain various type of natural products, they showed almost the same improve effects on abnormal lipid metabolism in traditional clinic. We suggested that different constituents of alleviates fever eliminating dampness Traditional Chinese Medicines act at different key target of lipid metabolism network to display intervention lipid metabolism through a multi-direction pattern. In this project, Five kind of most common used fever eliminating dampness Traditional Chinese Medicines, Scutellaria baicalensis, Coptis chinensis, Phellodendron chinense, Gentiana scabra and Sophora flavescens were selected as research objects, serum containing herb medicines will be administrated to oleic acid induced triglyceride accumulation liver cell lines, and then gene chip and antibody chip will be used to find the gene and protein expression difference, further, using a network pharmacology method, a multi-level structural network analysis method will be established to evaluate total effectiveness and relative relationship between targets of metabolism regulation effect, the key node and functional module will be confirmed. Next, combined with phytochemistry research result, using virtual screening and molecular docking method to predict pre-active constituent, and the regulation effects on lipid metabolism will be validated in vivo and in vitro. Finally, the mechanism and active compounds of fever eliminating dampness Traditional Chinese Medicines will be partly clarified and the common rule will be summarized. From above research, the new target for lipid metabolism regulation is hopeful to be found. The research results can also provide scientific evidence to Traditional Chinese Medicine clinical rational administration and new drug development.
