基于靶向脂质组学和蛋白组学的姜黄降脂作用机制研究

Hyperlipidemia has become an important risk factor leading to cardiovascular and cerebrovascular diseases, metabolic syndrome and other chronic diseases. Curcuminoids, a major type of chemical components in turmeric, demonstrate significant lipid-lowering activity and efficacy for prevention of atherosclerosis. However, the underlying mechanism of lipid-lowering effect remains unclear. Our previous study found that turmeric could significantly reverse the elevated serum level of lysophosphatidylcholine with a higher degree of unsaturation in the fatty acid chain in hyperlipidemia mice. In order to further elucidate the regulation of curcuminoids on lipid metabolism disorder and detailed mechanism of lipid-lowering effect, the project will integrate lipidomics and proteomics to monitor the dynamic changes of different lipid components and proteins in cell line and animal models to accurately and effectively identify key differential lipids and proteins. Then, the different profile of lipid, protein and phosphorylation protein will be analyzed to construct the network between lipid and protein, which can reveal the signal pathway of lipid-lowering effect of curcuminoids. Finally, key pathway of lipid-lowering will be verified through molecular biology method, thus the lipid-lowering mechanism of curcuminoids will be systematically elucidated. This study will not only provide a scientific basis for the application of turmeric in lipid lowering, but also offer new ideas for the study of pharmacological mechanism of active ingredients from traditional Chinese medicine.

高脂血症是导致心脑血管疾病、代谢综合症及其他慢性疾病的重要危险因素。姜黄中主要化学成分姜黄素类化合物具有显著的降脂活性及预防动脉粥样硬化的功效，但其降脂作用机制尚不明确。项目组前期研究发现姜黄能显著回调高脂血症小鼠血清中侧链为多不饱和脂肪酸的溶血磷脂酰胆碱水平。为了进一步阐明姜黄素类化合物对脂代谢紊乱的整体调控作用及其降脂机制，本项目将整合靶向脂质组学和蛋白组学研究手段，监测细胞和动物水平不同类别脂质成分和蛋白的动态变化，更准确有效地发现差异脂质成分和蛋白。随后整合分析脂质成分差异谱、蛋白表达差异谱和磷酸化修饰差异谱，构建脂质、蛋白及脂质与蛋白之间的作用网络，进而揭示姜黄素类化合物降脂的分子作用通路。最后通过分子生物学方法对其降脂作用的关键通路进行验证，从而系统阐明姜黄素类化合物的降脂作用机制。本研究将为姜黄在降脂方面的应用提供科学依据，也为中药活性成分药效机制研究提供新思路。

高脂血症是导致心脑血管疾病、代谢综合症及其他慢性疾病的重要危险因素。姜黄中主要化学成分姜黄素类化合物具有显著的降脂活性及预防动脉粥样硬化的功效，但其降脂作用机制尚不明确。为了阐明姜黄素类化合物对脂代谢紊乱的整体调控作用及其降脂机制，本项目将整合靶向脂质组学和蛋白组学研究手段，监测动物水平不同类别脂质成分和蛋白质的动态变化，更准确有效地发现了差异脂质成分和蛋白。随后整合分析脂质成分差异谱、蛋白表达差异谱，构建脂质、蛋白及脂质与蛋白之间的作用网络，进而揭示了姜黄素类化合物降脂的分子作用通路。最后通过分子生物学方法对其降脂作用的关键通路进行了验证，从而系统阐明了姜黄素类化合物的降脂作用机制。本研究为姜黄在降脂方面的应用提供科学依据，也为中药活性成分药效机制研究提供了新思路。