药学学报, 2018, 53(10): 1680-1688
引用本文:
魏紫奕, 徐文娟, 董姣姣, 刘洁, 贾志鑫, 陈奕君, 王明霞, 阳娇, 肖红斌. 羟基红花黄色素A对动脉粥样硬化早期脂肪酸的调控研究[J]. 药学学报, 2018, 53(10): 1680-1688.
WEI Zi-yi, XU Wen-juan, DONG Jiao-jiao, LIU Jie, JIA Zhi-xin, CHEN Yi-jun, WANG Ming-xia, YANG Jiao, XIAO Hong-bin. Hydroxysafflor yellow A repairing the metabolic disturbances of early atherosclerosis based on fatty acid profiling[J]. Acta Pharmaceutica Sinica, 2018, 53(10): 1680-1688.

羟基红花黄色素A对动脉粥样硬化早期脂肪酸的调控研究
魏紫奕1,2, 徐文娟2,3, 董姣姣1,2, 刘洁2,4, 贾志鑫2,4, 陈奕君1,2, 王明霞1,2, 阳娇1,2, 肖红斌2,4
1. 北京中医药大学中药学院, 北京 100029;
2. 北京中医药大学中药分析与转化研究中心, 北京 100029;
3. 北京中医药大学生命科学学院, 北京 100029;
4. 北京中医药大学北京中医药研究院, 北京 100029
摘要:
动脉粥样硬化(atherosclerosis,AS)是一种严重危害人类健康的复杂代谢紊乱综合征,其发生发展与游离脂肪酸(free fatty acid,FFA)代谢轮廓改变直接相关。本文采用氧化低密度脂蛋白(ox-LDL)诱导的泡沫化巨噬细胞作为动脉粥样硬化的早期模型,采用靶向代谢组学方法研究游离脂肪酸的代谢轮廓变化以及羟基红花黄色素A(hydroxysafflor yellow A,HSYA)的调控作用。通过动态多反应监测模式(dynamic MRM)在20 min内实现细胞内27种脂肪酸的定量分析,明确27种脂肪酸的含量分布。结合模式识别筛选出13个巨噬细胞泡沫化生物标志物,其中在巨噬细胞泡沫化过程中饱和脂肪酸总量升高,而十二碳酸、十四碳酸、十八碳烯酸及单不饱和脂肪酸总量降低,羟基红花黄色素A对十二碳酸、十四碳酸和十八碳烯酸异常代谢具有回调作用,网络分析表明与之相关的通路为脂肪酸生物合成通路(de novo fatty acid biosynthesis),oleoyl-(acyl-carrier-protein)hydrolase(OLAH)可能是羟基红花黄色素A调控脂肪酸代谢的潜在靶点。
关键词:    代谢组学      游离脂肪酸      巨噬细胞泡沫化      动脉粥样硬化      羟基红花黄色素A      脂肪酸生物合成     
Hydroxysafflor yellow A repairing the metabolic disturbances of early atherosclerosis based on fatty acid profiling
WEI Zi-yi1,2, XU Wen-juan2,3, DONG Jiao-jiao1,2, LIU Jie2,4, JIA Zhi-xin2,4, CHEN Yi-jun1,2, WANG Ming-xia1,2, YANG Jiao1,2, XIAO Hong-bin2,4
1. Schoolof Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China;
2. Research Center for Chinese Medicine Analysis and Transformation, Beijing University of Chinese Medicine, Beijing 100029, China;
3. School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China;
4. Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
Abstract:
Atherosclerosis (AS) is a complex metabolic syndrome that seriously harms human health, and its occurrence and development are directly related to the metabolic disturbances of free fatty acids (FFA). In this study, macrophage-derived foam cells were established as the model of early AS. Therefore, the metabolic disturbances of FFA in ox-LDL induced foamy macrophages were analyzed using target metabolomics. Then the effect of hydroxysafflor yellow A (HSYA) on regulating FFA was also explored. The quantitative analysis of 27 fatty acids was obtained within 20 min based on dynamic MRM mode. Thirteen metabolic biomarkers of macrophage-derived foam cells were identified using multivariate statistical analysis. It was found that upregulation of total SFA and downregulation of C12:0, C14:0, C18:1, total MUFA were the typical metabolic features in macrophage-derived foam cells. Furthermore, HSYA displayed obvious repairing effect on C12:0, C14:0 and C18:1, which were involved in de novo fatty acid biosynthesis pathway. Oleoyl-(acyl-carrier-protein) hydrolase (OLAH), as the key enzyme in de novo fatty acid biosynthesis pathway, may be a drug target of HSYA.
Key words:    metabolomics    free fatty acid    macrophage-derived foam cell    atherosclerosis    hydroxysafflor yellow A    de novo fatty acid biosynthesis   
收稿日期: 2018-06-03
DOI: 10.16438/j.0513-4870.2018-0409
基金项目: 国家自然科学基金青年科学基金资助项目(81703947).
通讯作者: 肖红斌,Tel:86-10-64286490,E-mail:hbxiao69@163.com
Email: hbxiao69@163.com
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