苦寒中药黄柏调节机体能量代谢的性效表征和机制研究
投稿时间:2024-09-25  修订日期:2024-10-15   点此下载全文
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臧梦楠* ZANG Mengnan 黑龙江中医药大学 Graduate School of Heilongjiang University of Traditional Chinese Medicine fsui@icmm.ac.cn 
孟晶 MENG Jing 中国中医科学院中药研究所 Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences 1665739321@qq.com 
谢冉 Xie Ran 中国中医科学院中药研究所 Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences 1831464491@qq.com 
宋琦 SONG Qi 中国中医科学院中药研究所 Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences qsong@icmm.ac.cn 
刘星 LIU Xing 黑龙江中医药大学 Graduate School of Heilongjiang University of Traditional Chinese Medicine 1696878341@qq.com 
高旅 GAO Lv 中国中医科学院中药研究所 Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences lgao@icmm.ac.cn 
窦宝凯 DOU Baokai 中国中医科学院中药研究所 Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences bkdou@icmm.ac.cn 
霍海如 HUO Hairu 中国中医科学院中药研究所 Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences hrhuo@icmm.ac.cn 
隋 峰 SUI Feng 中国中医科学院中药研究所 Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences suifeng2136@126.com 
基金项目:中国中医科学院科技创新工程项目(CI2021A03803);国家自然科学基金面上项目(No.82173998; 82374057)
中文摘要:目的 通过寒热趋向性测试分析探讨苦寒中药黄柏对机体的能量代谢的影响,并利用代谢组学技术探索内源性代谢产物的变化、揭示临床常用中药黄柏的苦寒药性的分子作用机理。方法 分别灌胃实验小鼠适量黄柏水煎液、生理盐水(对照组),按照一定时间间隔观测动物整体状态,并基于冷热板差示法观察小鼠温度趋向性变化;采用UPLC-MS技术,基于精确相对分子质量和碎片离子分析,检测和明确不同组别小鼠血清中内源性代谢产物的水平,主成分分析、偏最小二乘判别分析、正交偏最小二乘判别分析等数据分析方法用于比较和寻找灌胃黄柏水煎液和生理盐水小鼠血清的图谱和差异代谢物;采用Cytoscape 和 Metscape 软件对差异代谢物进行了网络模块化分析,寻找可能的分子作用靶标。结果 与对照组相比,黄柏组小鼠体温有明显下降趋势,从第二天开始出现显著差异(P<0.01);温度趋向性研究结果显示,给药后小鼠停留在高温区比例均有所升高,其中第一天与对照组相比有显著差异(P<0.05);对比对照组与黄柏组血清中内源性代谢产物,共发现19个差异代谢物,差异代谢物节点度值大于均值的有花生四烯酸、亚油酸和棕榈酸等;通过相关代谢通路分析,差异代谢物所参与构建的主要为花生四烯酸代谢通路、亚油酸代谢通路和不饱和脂肪酸生物合成通路,其中花生四烯酸代谢通路、亚油酸代谢通路在代谢组学网络模块图中占比最大。结论 通过调节花生四烯酸、亚油酸、棕榈酸、异柠檬酸等分子靶点和关联生物网络进而下调机体能量代谢的整体状态可能是黄柏表征苦寒药性的分子机制之一。
中文关键词:黄柏  能量代谢  温度趋向  内源性产物  代谢通路
 
Characterization of the mechanism of Phellodendri Chinensis Cortex regulating body energy metabolism
Abstract:Objective This study was conducted to evaluate the coldness-hotness property of Phellodendri Chinensis Cortex and explore its molecular mechanism of efficacy by observing the coldness-hotness tendency behavior of herb-administrated mice as well as exploring it’s effect on serum metabolites in mice using metabolomics technology, aiming to search for the related biomarkers, metabolic pathways and related targets that are closely related to the clinical therapeutic effect of Phellodendri Chinensis Cortex. Methods The mice were randomly divided into control group and drug administration group, which were respectively intragastrically administrated with distilled water and Phellodendri Chinensis Cortex decoction. The coldness-hotness tendency of experimental mice were tested and analyzed by applying a gradient hot plate method; the blood samples from mice of the two groups were analyzed by UPLC-MS/MS. The principal component analysis, partial least squares discrimination analysis and orthogonal partial least squares discrimination analysis were selected to screen differential metabolites and analyze metabolic pathways based on the exact molecular weights and fragment ion analysis. In order to screen differential potential targets, Cytoscape and Metascape software were used to establish the network modularization analysis of differential metabolites. Results Compared with the control group, the body temperature of mice in the Phellodendri Chinensis Cortex group showed a significant downward trend, with significant differences observed from the second day onward (P<0.01); the results of the temperature preference study showed that the proportion of mice staying in the high-temperature zone increased after administration, and there was a significant difference
keywords:Phellodendri Chinensis Cortex  energy metabolism  temperature tendency  endogenous metabolites  metabolic pathway
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