机构地区:[1]福建中医药大学中医学院,福州350122 [2]中医证研究福建省高校重点实验室,福州350122 [3]福建省立医院,福州350001 [4]厦门大学生命科学学院,厦门361005 [5]上海交通大学医学院附属瑞金医院,上海200000 [6]福建省中医健康状态辨识重点实验室,福州350122 [7]福建中医药大学中西医结合学院,福州350122
出 处:《中华中医药杂志》2023年第5期1996-2003,共8页China Journal of Traditional Chinese Medicine and Pharmacy
基 金:国家自然科学基金项目(No.81873234,No.81273666);福建省卫生教育联合攻关计划项目(No.2019-WJ-39);福建省自然科学基金面上项目(No.2021J01891)。
摘 要:目的:利用UHPLC-QE-MS代谢组学技术筛选代谢综合征(MS)痰证可能的特征标志物,从代谢角度初步探讨二陈汤改善MS痰证的机制,为寻找化痰的靶点提供参考依据。方法:50只SPF级雄性Wistar大鼠随机分成空白组12只,造模组38只,以高糖高盐高脂饮食喂养12周复制MS痰证大鼠模型。检测大鼠的一般状况、生长、血压、糖脂代谢情况,根据模型评价标准筛选成模大鼠,将24只成模大鼠随机分为模型组和二陈汤组各12只,二陈汤组予二陈汤5.3 g/kg灌胃,模型组及空白组予0.9%氯化钠溶液10.5 mL/kg灌胃,每日1次,连续4周。收集第16周末空白组(9只)、模型组(8只)和二陈汤组(9只)大鼠血清。利用LC-MS技术进行检测,对数据进行分析以筛选差异代谢产物,并登入京都基因与基因组百科全书数据库整理出差异代谢产物映射的所有通路,通过对差异代谢物所在通路的富集和拓扑分析,寻找差异代谢通路。结果:以VIP>1且P<0.05为卡值,空白组和模型组最终鉴定出357种差异代谢产物;模型组和二陈汤组最终鉴定出109种差异代谢产物。空白组-模型组与模型组-二陈汤组,P<0.05或影响因子>0的共同代谢通路分别是甘氨酸、丝氨酸和苏氨酸代谢,丙氨酸、天冬氨酸和谷氨酸代谢。空白组和模型组共同的代谢通路命中的差异代谢产物为甘氨酸、L-丝氨酸、D-丝氨酸、L-苏氨酸、L-天冬氨酸、L-别苏氨酸、肌酸;模型组和二陈汤组则为二甲基甘氨酸、肌酸和琥珀半醛。结论:甘氨酸、L-丝氨酸、D-丝氨酸、L-苏氨酸、L-天冬氨酸、L-别苏氨酸、肌酸可能是MS痰证的特征标志物,二甲基甘氨酸、肌酸和琥珀半醛等代谢产物则与二陈汤化痰作用紧密相关,其所在代谢通路可能是治疗痰证潜在切入点。Objective:To use UHPLC-QE-MS metabolomics technology to screen the possible metabolic markers of metabolic syndrome(MS)phlegm syndrome,to preliminarily explore the mechanism of Erchen Decoction in the treatment of MS phlegm syndrome from the perspective of metabolism,and to provide reference for finding therapeutic targets for resolving phlegm.Methods:Fifty SPF male Wistar rats were randomly divided into control group(n=12)and model group(n=38).They were fed with high-sugar,high-salt and high-fat diet for 12 weeks to replicate the MS phlegm syndrome rat model.The general condition,growth,blood pressure,and glucose and lipid metabolism of the rats were detected,and the model rats were screened according to the model evaluation standard.The group was given Erchen decoction 5.3 g/kg by gavage,and the model group and the control group were given normal saline 10.5 mL/kg by gavage,once a day for 4 consecutive weeks.The serum of rats in control group(n=9),model group(n=8)and Erchen decoction group(n=9)at the end of 16th week was collected.UHPLCQE-MS technology was used for detection,data was analyzed to screen differential metabolites,and all the pathways mapped by differential metabolites were sorted out by logging into the Kyoto Encyclopedia of Genes and Genomes database.Topological analysis to find differential metabolic pathways.Results:Taking VIP>1 and P<0.05 as the threshold value,357 differential metabolites were finally identified in the control group and the model group;109 differential metabolites were finally identified in the model group and Erchen decoction group.The control group-model group and the model group-Erchen decoction group,the common metabolic pathways of influencing factors>0 or P<0.05 are glycine,serine and threonine metabolism,alanine,aspartate and glutamate metabolism.The differential metabolites hit by the common metabolic pathways of the control group and the model group were glycine,L-serine,D-serine,L-threonine,L-aspartic acid,L-Allothreonine,and creatine;the model group and Erchen deco
分 类 号:R259[医药卫生—中西医结合]
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