摘要
目的通过非靶向代谢组学技术,分析腹膜功能障碍长程腹膜透析(peritoneal dialysis,PD)患者与腹膜功能正常短程PD患者透出液差异代谢物及代谢途径,寻找腹膜纤维化(peritoneal fibrosis,PF)潜在的代谢生物标志物及干预靶点。方法纳入PD患者26人,分为腹膜功能障碍(2.5%腹膜透析液4 h净超滤<100 ml)长程组(透析龄>6年,n=13),腹膜功能正常短程组(透析龄<12月,n=13),收集患者的人口学及临床数据,采用液相色谱-串联质谱联用技术对患者的透出液进行检测及分析,筛选差异代谢物,并行代谢通路注释及富集分析。结果:与短程组相比,长程组血清白蛋白更低(t=-2.320,P=0.029)、血清肌酐(t=2.723,P=0.012)及尿素氮(t=2.231,P=0.026)水平更高。长程组4 h超滤量更少(t=-8.308,P<0.001),4h透析液/血浆肌酐值(dialysat/plasma creatinine,D/Pcr)更高(t=3.037,P=0.006)。相对于短程组,长程组表达上调有2040种代谢产物,表达下调有992种。在长程组腹透液代谢物表达增多的有2-酮丁酸、硫酸吲哚酚等。丝氨酸、左旋肉碱、丁内酯Ⅱ等代谢产物在短程组中表达更丰富。差异代谢物通路注释的结果显示集中在以苯丙氨酸代谢为主的氨基酸代谢,以及包括丙酸盐代谢、柠檬酸循环等在内的碳水化合物代谢。对代谢通路深入分析,苯丙氨酸代谢、甘油酸和二羧酸代谢、柠檬酸循环通路作为后续研究的重点。结论基于非靶向代谢组学对于长短程不同腹膜功能的PD透出液的差异代谢物及代谢途径分析,为寻找PF的生物标志物和干预靶点提供了关键信息和新的视角。
Objective Using untargeted metabolomics technology,this study analyzed the differential metabolites and metabolic pathways in the dialysate of long-term peritoneal dialysis(PD)patients with peritoneal dysfunction versus short-term PD patients with normal peritoneal function,and aimed to identify potential metabolic biomarkers and intervention targets for peritoneal fibrosis(PF).Methods A total of 26 PD patients were included and divided into two groups:the long-term group with peritoneal dysfunction(net ultrafiltration volume of 2.5%peritoneal dialysate at 4 hours<100 ml,dialysis vintage>6 years,n=13)and the shortterm group with normal peritoneal function(dialysis vintage<12 months,n=13).Demographic characteristics and clinical data of the patients were collected.Liquid chromatography-tandem mass spectrometry(LCMS/MS)was used to detect and analyze metabolites in the dialysate.The differential metabolites were screened.Metabolic pathway annotation and enrichment analysis were performed for the differential metabolites.Results Compared to the short-term group,the long-term group with peritoneal dysfunction had lower serum albumin(t=-2.320,P=0.029),and higher levels of serum creatinine(t=2.723,P=0.012)and blood urea nitrogen(t=2.231,P=0.026).The long-term group also showed lower 4-hour ultrafiltration volume(t=-8.308,P<0.001)and higher 4-hour dialysate-to-plasma creatinine ratio(D/Pcr)(t=3.037,P=0.006).Compared to the short-term group,the long-term group had 2040 up-regulated metabolites and 992 down-regulated metabolites.Furthermore,2-ketobutyric acid,indoxyl sulfate and other metabolites increased in the long-term group.Metabolites such as serine,L-carnitine,and butyrolactone II were more abundant in the short-term group.Pathway annotation of differential metabolites revealed enrichment in amino acid metabolism,mainly phenylalanine metabolism,and carbohydrate metabolism,including propionate metabolism,citric acid cycle,etc.Further analysis of the metabolic pathways identified phenylalanine metabolism,glycerate and dicarboxylic acid metabolism,and the citric acid cycle as key pathways for subsequent research.Conclusion The analysis of differential metabolites and metabolic pathways in the effluent of PD patients with different peritoneal functions based on non-targeted metabolomics provides key information and a new perspective for identifying biomarkers and intervention targets for PF.
作者
张悦
吕欣晨
华佳
蔡婷
刘斌
王鸿超
陆文伟
王凉
ZHANG Yue;LV Xin-chen;HUA Jia;CAI Ting;LIU Bin;WANG Hong-chao;LU Wen-wei;WANG Liang(Department of Nephrology,The Affiliated Wuxi People's Hospital of Nanjing Medical University,Wuxi 214023,China;School of Food Science and Technology,Jiangnan University,Wuxi 214122,China)
出处
《中国血液净化》
2025年第8期642-647,共6页
Chinese Journal of Blood Purification
基金
无锡市医学创新团队建设项目(CXTD2021010)。
关键词
腹膜透析
腹膜纤维化
非靶向代谢组学
代谢产物
代谢途径
Peritoneal dialysis
Peritoneal fibrosis
Non-targeted metabolomics
Metabolic products
Metabolic pathways
