摘要
目的:寻找与甲氨蝶呤治疗类风湿关节炎个体差异相关的生物标志物,从代谢调控角度解释甲氨蝶呤的个体差异。方法:选取2018年1月1日至2019年12月31日南京大学医学院附属鼓楼医院风湿免疫科接受甲氨蝶呤规范化治疗的成年类风湿关节炎患者,收集患者的临床信息,依据治疗前后28个关节疾病活动度-血沉(DAS28-ESR)评分划分成甲氨蝶呤治疗有效组(22例)和无效组(17例)。借助超高效液相-四极杆-飞行时间质谱法采集2组患者的血清代谢轮廓谱,采用主成分分析和偏最小二乘判别分析等方法进行数据处理,筛选出甲氨蝶呤治疗类风湿关节炎个体差异相关的生物标志物和代谢通路。结果:有效组和无效组患者接受甲氨蝶呤治疗前的红细胞沉降率、C反应蛋白和DAS28-ESR评分均无统计学差异;接受甲氨蝶呤治疗6个月后,有效组红细胞沉降率、C反应蛋白和DAS28-ESR评分显著低于无效组。甲氨蝶呤治疗有效组和无效组的血清代谢轮廊谱差异明显,与无效组相比,有效组9个差异代谢物水平下降,包括肉豆蔻酸、棕榈酸、色氨酸和尿苷等;27个代谢物水平上升,包括甘氨胆酸、鞘氨醇-1-磷酸、溶血磷脂酰胆碱和溶血磷脂酰乙醇胺等。这些差异代谢物主要聚焦于苯丙氨酸、酪氨酸和色氨酸生物合成、色氨酸代谢和酪氨酸代谢等通路。结论:该研究采用代谢组学方法,挖掘甲氨蝶呤治疗类风湿关节炎有效组和无效组内源性代谢物的差异,从代谢调控角度探讨了甲氨蝶呤的个体差异。
OBJECTIVE To find out the biomarkers associated with the response to methotrexate(MTX)therapy in rheumatoid arthritis(RA),and explain the individual differences of MTX therapy from the perspectives of metabolomics.METHODS RA patients who received MTX therapy from January 1,2018 to December 31,2019 in Rheumatology and Immunology Department of Affiliated Drum Tower Hospital of Nanjing University Medical School were enrolled in this study.The clinical data of patients were collected.The patients were divided into the effective and non-effective groups based on the difference of 28 joint disease activity-erythrocyte sedimentation rate(DAS28-ESR)scrore before and after MTX therapy.Ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry was adopted to acquire the serum profiles.Then principal component analysis and partial least squares-discriminant analysis were conducted to find out the biomarkers and metabolic pathways associated with the response to MTX therapy.RESULTS There was no significant difference in erythrocyte sedimentation rate,C-reactive protein,and DAS28-ESR score between the effective and non-effective groups before MTX therapy.After six months of MTX therapy,the effective group showed significantly lower erythrocyte sedimentation rate,C-reactive protein,and DAS28-ESR score as compared with the non-effective group.Obvious difference was shown in the metabolic profiles between the effective and non-effective groups.As compared with those in the non-effective group,the levels of nine differential metabolites(i.e.,myristic acid,palmitic acid,tryptophan and uridine,etc.)were reduced,while the levels of twenty-seven metabolites(i.e.,glycocholic acid,sphingosine 1-phosphate,lysophosphatidylcholine and lysophosphatidylethanolamine,etc.)were increased in the effective group.Those differential metabolites participated in phenylalanine,tyrosine and tryptophan biosynthesis,tryptophan metabolism,tyrosine metabolism and so on.CONCLUSION The study adopted metabolomics to mine the differen
作者
王敏
束庆
张天祺
罗雪梅
柳航
朱怀军
葛卫红
WANG Min;SHU Qing;ZHANG Tianqi;LUO Xuemei;LIU Hang;ZHU Huaijun;GE Weihong(Department of Pharmacy,Affiliated Drum Tower Hospital of Nanjing University Medical School,Jiangsu Nanjing 210008,China;Nanjing Clinical Pharmacy Center,Jiangsu Nanjing 210008,China)
出处
《中国医院药学杂志》
CAS
北大核心
2023年第17期1893-1898,1938,共7页
Chinese Journal of Hospital Pharmacy
基金
国家自然科学基金项目(编号:82204846)
江苏省医学创新团队项目(编号:CXTDA2017041)
南京市卫生科技发展专项资金-医学重点科技发展项目(编号:ZKX21016)
南京鼓楼医院临床研究专项资金(编号:2022-LCYJ-PY-14,2021-LCYJ-PY-37)
关键词
甲氨蝶呤
类风湿关节炎
个体差异
代谢组学
methotrexate
rheumatoid arthritis
individual difference
metabolomics
