摘要
目的了解鼠疫疫苗株EV76免疫后中国恒河猴血清代谢的改变,为评价其免疫效果提供科学依据。方法将6只恒河猴随机分为2组:EV76免疫组和对照组,每组3只(2雌1雄),免疫组每只动物经腹股沟皮下注射EV761.57×1010CFU,对照组经皮下注射等体积PBS。4周后经股静脉采血,采用超高液相色谱-质谱联用技术(ultraperformance liquid chromatography-tandem mass spectrometry,UPLC-MS/MS)进行血清非靶向代谢组学检测,按照代谢物的变量重要性投影(variable importance in projection,VIP)>1.0,差异倍数(fold change,FC)>1.5或<0.667,且P<0.05的标准进行差异代谢物筛选,并进行差异代谢物KEGG富集分析。结果共鉴定到正离子模式代谢物460个,负离子模式代谢物440个。经数据库比对,共发现24个差异代谢物;经KEGG通路富集分析,差异代谢物主要涉及甘氨酸、丝氨酸和苏氨酸代谢,苯丙氨酸、酪氨酸和色氨酸的生物合成,缬氨酸、亮氨酸和异亮氨酸的生物合成,苯丙氨酸、半胱氨酸和蛋氨酸、酪氨酸代谢。结论EV76通过增加乙酰左旋肉碱、D-谷氨酰胺、次黄嘌呤核苷、皮质醇等含量,发挥其免疫增强作用,同时存在多种氨基酸代谢通路的异常改变。
Objective To investigate the changes in serum metabolism of Chinese rhesus macaques after immunization with plague vaccine strain EV76,and to provide a scientific basis for evaluating the immunization effect of plague vaccine strain.Methods Six rhesus macaques were divided into EV76 immunization group and control group,with three in each group(two females and one male).The immunization group was injected with 1.57×10~(10)CFU EV76 subcutaneously in the groin,and the control group was only injected with the same amount of PBS subcutaneously.Four weeks later,the blood was collected from femoral vein,and serum non-targeted metabolomics was detected by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).Differential metabolites were screened according to the criteria of variable importance in projection(VIP)>1.0,fold change(FC)>1.5 or<0.667 and P<0.05,and KEGG enrichment analysis of differential metabolites was performed.Results A total of 460 metabolites in positive ion mode and 440 in negative ion mode were identified.A total of 24 differential metabolites were found after database comparison.According to KEGG pathway enrichment analysis,the differential metabolites were mainly involved in the metabolism of glycine,serine and threonine,the biosynthesis of phenylalanine,tyrosine and tryptophan,the biosynthesis of valine,leucine and isoleucine,the metabolism of phenylalanine,the metabolism of cysteine and methionine,and the metabolism of tyrosine.Conclusion EV76 exerts its immune-enhancing effect by increasing the content of acetyl-L-carnitine,D-glutamine,hypoxanthine nucleoside and cortisol,and there are abnormal changes in a variety of amino acid metabolic pathways.
作者
张琪
张爱萍
李强
张晓璐
王永顺
吴海生
张青雯
祁芝珍
赵志军
ZHANG Qi;ZHANG Aiping;LI Qiang;ZHANG Xiaolu;WANG Yongshun;WU Haisheng;ZHANG Qingwen;QI Zhizhen;ZHAO Zhijun(NHC Key Laboratory of Plague Prevention and Control,Qinghai Institute for Endemic Disease Prevention and Control,Xining 810021,Qinghai Province,China;不详)
出处
《中国生物制品学杂志》
2025年第11期1292-1298,共7页
Chinese Journal of Biologicals
基金
2023年度青海省“昆仑英才·科技领军人才”自然科学与工程技术学科带头人培养项目
2023年度青海省“昆仑英才·高端创新创业人才”培养领军人才项目。
关键词
鼠疫疫苗株EV76
恒河猴
血清
代谢
Plague vaccine strain EV76
Rhesus macaques
Serum
Metabolism
