海洋真菌次生代谢产物Xyloketal B对AS抗氧化应激治疗的脂代谢组学研究

项目名称： 海洋真菌次生代谢产物Xyloketal B对AS抗氧化应激治疗的脂代谢组学研究

项目编号： No.81202454

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 项琪

作者单位： 暨南大学

项目金额： 24万元

中文摘要： 本项目前期实验发现来自海洋真菌代谢产物的Xyloketals结构新颖，对apoE缺陷小鼠具有高效的抗动脉粥样硬化（AS）作用，与辛伐他汀相比优势显著，是一个很有潜力的治疗AS新化合物。脂质平衡功能失调在AS病变发生发展中起着关键作用。脂代谢组学对探求AS病因和明确药物的治疗效果意义重大。Xyloketals有别于其他治疗药物的全新结构可能预示着全新的脂质代谢调控过程。本项目从代谢组学入手结合生物信息学手段，收集药物干预后apoE小鼠血清和主动脉，用液相色谱串联离子阱飞行时间质谱(LC/MS-IT-TOF)分离鉴定脂质代谢物，主成分分析法(PCA)和偏最小二乘法(PLS-DA)对正常组、模型组和治疗组的脂质代谢物进行模式识别，筛选出特异性脂生物标记物，作为靶点探讨Xyloketals对AS治疗中与脂质代谢相关的分子机制。该研究将为AS的疗效提供新的评价靶标，也推动海洋创新药物的研究开发。

中文关键词： xylokeltal B；脂代谢；靶点；信号通路；肝药酶代谢

英文摘要： Previous studies suggested Xyloketals isolated from marine mangrove endophytic fungus were a series of novel products with unique structure. Xyloketals showed a more super and more efficient activities of anti-atherosclerosis in the Apolipoprotein E-deficient mice than simvastatin. The remarkable anti-atherosclerosis effect may serve the Xyloketals as a promising treatment of this disease. Dysregulation of lipid homeostasis plays a central role in occurrence and development of AS. The study of lipid metabolism has become critical for exploring the etiology of AS and clarifying the validation of drugs. The project selected apoE deficient mice and collected animal serum and aorta after Xyloketals intervention. An analytical method was developed to identification lipid metabolites by LC/MS-IT-TOF. PCA and PLS-DA methods were carried out to recognize the pattern of animal lipid metabolites in the control group, model group and treatment group and then select specific lipid biomarker as a target which can be used to explore the molecular mechanism correlated with lipid metabolism on the treatment of atherosclerosis using Xyloketals. This study substantiates the content of Xyloketals basic research and confirms the potential for using Xyloketals to treat AS from lipidomics aspect.

英文关键词： xylokeltal B；lipid metabolism；drug targets；signal pathway；liver P450 enzyme