基于内源性代谢物探讨黄芩苦寒药性分子作用机制  

Exploration on the Molecular Mechanism of Bitter-cold Property of Scutellaria Radix Based on Endogenous Metabolites

作　　者：刘星 宋琦 谢冉 孟晶[2] 臧梦楠 张焕焕 宋海津 张淼[1] 霍海如[2] 隋峰[2] LIU Xing;SONG Qi;XIE Ran;MENG Jing;ZANG Mengnan;ZHANG Huanhuan;SONG Haijin;ZHANG Miao;HUO Hairu;SUI Feng(School of Basic Medicine,Heilongjiang University of Chinese Medicine,Harbin 150040,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]黑龙江中医药大学基础医学院,黑龙江哈尔滨150040 [2]中国中医科学院中药研究所,北京100700

出　　处：《中国中医药信息杂志》2025年第4期128-134,共7页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(82173998、82374057);中国中医科学院科技创新工程(CI2021A03803)。

摘　　要：目的在评测苦寒中药黄芩寒热药性的基础上,寻找表征其苦寒药性的生物标志物,以及可能代谢途径和相关靶点,探讨其分子作用机制。方法将40只小鼠随机分为对照组和给药组,分别灌胃生理盐水和黄芩水煎液,连续4 d,采用冷热板差示法评价小鼠的寒热趋向;采用超高效液相色谱串联质谱技术分析小鼠血液样本,采用主成分分析、偏最小二乘-判别分析、正交偏最小二乘-判别分析方法筛选差异代谢物,并进行代谢通路分析;使用Cytoscape3.9.0软件对差异代谢物进行网络模块化分析,寻找可能的分子作用靶点。结果给药组小鼠于给药第2日肛温下降,与对照组比较差异有统计学意义(P<0.01);寒热趋向性测试中,给药组小鼠整体表现为高温趋向性增强,高温区停留比例增加,给药第2、3日与对照组比较差异有统计学意义(P<0.01,P<0.05);血清代谢组数据模式识别分析显示,给药组与对照组血清样本能够完全分离,共筛选出14个差异代谢物;代谢通路分析得出16条相关通路,包括不饱和脂肪酸生物合成,亚油酸代谢,柠檬酸循环(TCA循环),花生四烯酸代谢,甘氨酸、丝氨酸和苏氨酸代谢,甾体激素生物合成等;网络模块化分析共得到16个模块,其中花生四烯酸代谢通路和亚油酸代谢通路模块较大;花生四烯酸、亚油酸节点度值大于均值,涉及花生四烯酸代谢、亚油酸代谢通路;通过筛选关联到细胞色素P450酶系中的26个基因。结论苦寒中药黄芩可能通过干预花生四烯酸、亚油酸等代谢途径,进而调控机体能量代谢,实现其生物效应和药性表征。Objective To identify biomarkers that characterize its bitter-cold properties of Scutellaria Radix on the basis of evaluating its cold and hot properties,as well as possible metabolic pathways and related targets;To explore its molecular mechanism.Methods Totally 40 mice were randomly divided into a control group and a treatment group,and were orally administered with normal saline and Scutellaria Radix decoction,respectively,for 4 consecutive days.The cold and hot plate differential method was used to evaluate the cold and hot tendencies of the mice;UPLC-MS/MS technology was used to analyze mouse blood samples,differential metabolites were screened using principal component analysis,partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis methods,and metabolic pathway analysis was performed;network modular analysis of differential metabolites was performed using Cytoscape 3.9.0 software to identify potential molecular targets.Results On the second day of administration,the anal temperature of mice in the treatment group decreased significantly compared to the control group(P<0.01);in the cold and hot tendency test,the mice in the treatment group showed an overall increase in high-temperature tendency and a higher proportion of high-temperature zone retention.There was a statistically significant difference(P<0.01,P<0.05)between the treatment group and the control group on the 2nd and 3rd day of treatment;the pattern recognition analysis of serum metabolome data showed that the serum samples of the treatment group and the control group could be completely separated,and a total of 14 differential metabolites were screened out;metabolic pathway analysis identified 16 related pathways,including unsaturated fatty acid biosynthesis,linoleic acid metabolism,citric acid cycle(TCA cycle),arachidonic acid metabolism,glycine,serine and threonine metabolism,steroid hormone biosynthesis,etc.;a total of 16 modules were obtained through network modular analysis,among which the arac

关 键 词：黄芩 内源性代谢物 花生四烯酸代谢 亚油酸代谢 代谢组学 

分 类 号：R285.1[医药卫生—中药学]