糖尿病合并骨质疏松症及肝肾亏虚证型的代谢组学研究  

Metabolomics of diabetes mellitus complicating with osteoporosis and syndrome of liver-kidney deficiency

作　　者：牛忻烨 俞璐[1] 高俊[1] 翟羽[1] NIU Xinye;YU Lu;GAO Jun;ZHAI Yu(Changzhou Hospital Affiliated to Nanjing University of Chinese Medicine,Changzhou 213000,Jiangsu,China;Nanjing University of Chinese Medicine,Nanjing 210000,Jiangsu,China)

机构地区：[1]南京中医药大学常州附属医院,江苏常州213000 [2]南京中医药大学,江苏南京210000

出　　处：《现代中西医结合杂志》2025年第4期445-458,共14页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：国家自然科学基金资助项目(82374479);常州市卫健委科技项目(QN 202044)。

摘　　要：目的探讨糖尿病性骨质疏松症(DOP)肝肾亏虚证和非肝肾亏虚证患者的代谢组学特征,为中医辨病辨证客观化提供参考依据。方法以2022年6月—2023年2月在常州市中医医院骨伤科和内分泌科诊治的40例DOP患者和20例糖尿病患者作为研究对象,采用随机数字法随机抽样,最终取6例糖尿病患者(糖尿病组)、16例DOP患者(DOP组)(其中DOP肝肾亏虚证患者8例为DOP肝肾亏虚证组,DOP非肝肾亏虚证患者8例为DOP非肝肾亏虚证组)的血清样本,采用超高效液相色谱-质谱技术检测血清代谢物含量,采用主成分分析(PCA)、正交偏最小二乘法判别分析(OPLS-DA)等多元统计方法筛选组间差异代谢物,并对差异代谢物进行鉴定、统计分析、层次聚类分析、KEGG注释及代谢通路分析。结果DOP组和糖尿病组患者血清代谢物中PE(20∶1(11Z)/14∶1(9Z))、PE(18∶0/18∶2)、2-Linoleoyl-1-palmitoyl-sn-glycero-3-phosphoethanolamine等物质代谢具有显著差异,并在次生代谢物合成、脂肪酸代谢、逆行内源性大麻素信号传导、黄酮类合成、小分子化合物降解等代谢通路富集上存在差异。DOP肝肾亏虚证组和DOP非肝肾亏虚证组患者血清代谢物中PC(18∶0/14∶0)、Oxybutynine、17beta-dihydroequilin、1,2-Dilinoleoyl-sn-glycero-3-phosphoethanolamine等物质代谢具有显著差异,并在微生物代谢、色氨酸和酪氨酸等氨基酸代谢、芳香族化合物降解等代谢通路富集上存在差异。结论DOP肝肾亏虚证患者、DOP非肝肾亏虚证患者及糖尿病患者之间血清代谢物存在差异,且代谢通路及作用机制也有明显差异,为中医药治疗该证型DOP提供了可能的靶点。Objective It is to explore the metabolomics characteristics of diabetic osteoporosis(DOP)patients with or without syndrome of liver-kidney deficiency,and to provide some references for the objectification of traditional Chinese medicine syndrome differentiation and disease differentiation.Methods Forty DOP patients and 20 diabetes mellitus patients diagnosed and treated in the Department of Orthopedics and Traumatology and the Department of Endocrinology of Changzhou Hospital of Traditional Chinese Medicine from June 2022 to February 2023 were collected as the study subjects,and they were randomly selected by the random number method,finally,the serum specimens were taken from 6 diabetes mellitus(DM)patients(DM group),16 DOP patients(DOP group) among which 8 DOP patients with syndrome of liver-kidney deficiency as DOP liver-kidney deficiency syndrome group,and 8 cases without syndrome of liver-kidney deficiency as DOP non-liver-kidney deficiency syndrome group.The contents of serum metabolites were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)technology,and the differential metabolites among the groups were screened by multivariate statistical methods such as principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA),then the differential metabolites were identified,statistically analyzed,hierarchically clustered,and annotated with KEGG,as well as analyzed for metabolic pathways.Results There were significant differences in the metabolism of substances in the serum metabolites such as PE(20∶1(11Z)/14∶1(9Z)),PE(18∶0/18∶2),and 2-Linoleoyl-1-palmitoyl-sn-glycero-3-phosphoethanolamine,and there were differences in the enrichments of metabolic pathways such as secondary metabolite synthesis,fatty acid metabolism,retrograde endocannabinoid signaling,flavonoid synthesis,and small molecule compound degradation between DOP group and DM group.There were significant differences in the metabolism of substances in the serum meta

关 键 词：糖尿病性骨质疏松症 糖尿病 中医证型 代谢组学 生物标志物 

分 类 号：R587.1[医药卫生—内分泌]