骨关节炎大鼠尿液潜在生物标志物及代谢通路筛选  

Screening of potential biomarkers and metabolic pathways in urine of rats with osteoarthritis

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作  者:王雨萌 王丽华 Wang Yumeng;Wang Lihua(Medical Record and Statistics Room of Ningbo Beilun People's Hospital,Zhejiang Province,Ningbo 315800,China;Key Laboratory of Etiology and Epidemiology,National Health Commission&Education Bureau of Heilongjiang Province,Center for Endemic Disease Control,Chinese Center for Disease Control and Prevention,Harbin Medical University,Harbin 150081,China)

机构地区:[1]浙江省宁波市北仑区人民医院病案统计室,宁波315800 [2]哈尔滨医科大学中国疾病预防控制中心地方病控制中心,国家卫生健康委病因流行病学重点实验室,黑龙江省普通高校病因流行病学重点实验室,哈尔滨150081

出  处:《中华地方病学杂志》2025年第3期192-197,共6页Chinese Journal of Endemiology

基  金:国家自然科学基金(81372937)。

摘  要:目的筛选与骨关节炎相关的差异代谢物及其代谢通路,为深入研究骨关节炎生物标志物提供线索。方法采用成组设计,将60只雄性SD大鼠(体质量为300~350 g)按照随机数字表法分为模型组和对照组,每组30只。实验周期分别为4、8和12周,每个周期每组10只大鼠。模型组大鼠左侧膝关节行改良Hulth法手术,5 d后,驱赶大鼠使之活动,每天30 min。实验期满,收集两组大鼠24 h尿液。采用超高效液相色谱-四级杆-飞行时间质谱仪检测尿液中的小分子代谢物,并通过多元统计分析及数据库比对,筛选与骨关节炎相关的差异代谢物及代谢通路。结果共筛选出9个与骨关节炎相关的尿液差异代谢物。其中,实验4周时筛选出9个,与对照组比较,模型组犬尿氨酸、柠檬酸、磺基丙氨酸、丙二酰肉碱、泛醌-2、L-胱硫醚和L-天冬氨酸水平均较高[26317(19439,33297)比3595(512,23556)、7137(2901,9252)比1854(660,4754)、6625±4468比3006±2636、4254(2949,7850)比2223(1230,3390)、14558(6605,26047)比5908(1172,10560)、4492(2541,33796)比1038(885,2938)、3038±2282比1286±1264],而5-L-谷氨酰基牛磺酸和S-腺苷甲硫氨酸水平均较低(2145±658比6457±5457、872±582比5572±5362,均P<0.05);实验8周时筛选出7个,与对照组比较,模型组犬尿氨酸、柠檬酸、磺基丙氨酸、5-L-谷氨酰基牛磺酸、丙二酰肉碱和泛醌-2水平均较高,而L-胱硫醚水平较低(均P<0.05);实验12周时筛选出4个,与对照组比较,模型组5-L-谷氨酰基牛磺酸水平较高,而犬尿氨酸、柠檬酸和磺基丙氨酸水平均较低(均P<0.05)。筛选出2条与骨关节炎相关的代谢通路,分别为半胱氨酸和蛋氨酸代谢通路、精氨酸和脯氨酸代谢通路,其中,磺基丙氨酸、S-腺苷甲硫氨酸和L-胱硫醚归属于半胱氨酸和蛋氨酸代谢通路,L-天冬氨酸和S-腺苷甲硫氨酸归属于精氨酸和脯氨酸代谢通路。结论犬尿氨酸、柠檬酸、磺基丙氨酸和5-L-谷氨�Objective To screen differential metabolites and their metabolic pathways related to osteoarthritis,and to provide clues for further study of biomarkers of osteoarthritis.Methods Using group design,60 male SD rats(weighting 300-350 g)were divided into a model group and a control group according to random number table method,with 30 rats in each group.The experimental periods were 4,8 and 12 weeks,respectively,with 10 rats per group per period.The left knee joint of rats of the model group rats underwent modified Hulth method surgery.After 5 days,the rats were driven to move for 30 minutes a day.At the end of the experiment,24 h urine of rats in two groups was collected.Small molecule metabolites in urine were detected by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometer,and the differential metabolites and metabolic pathways related to osteoarthritis were screened by multivariate statistical analysis and database comparison.Results A total of 9 differential metabolites associated with osteoarthritis were screened out in urine.Among them,9 metabolites were screened out at 4 weeks of the experiment.Compared with the control group,the model group had higher levels of kynurenine,citric acid,cysteic acid,malonyl carnitine,ubiquinone-2,L-cystathionine and L-aspartic acid[26317(19439,33297)vs 3595(512,23556),7137(2901,9252)vs 1854(660,4754),6625±4468 vs 3006±2636,4254(2949,7850)vs 2223(1230,3390),14558(6605,26047)vs 5908(1172,10560),4492(2541,33796)vs 1038(885,2938),3038±2282 vs 1286±1264],while the levels of 5-L-glutamyltaurine and S-adenosylmethionine were lower(2145±658 vs 6457±5457,872±582 vs 5572±5362,P<0.05).At 8 weeks of the experiment,7 metabolites were screened out.Compared with the control group,the model group had higher levels of kynurenine,citric acid,cysteic acid,5-L-glutamyltaurine,malonyl carnitine and ubiquinone-2,while the level of L-cystathionine was lower(P<0.05).At 12 weeks of the experiment,4 metabolites were screened out.Compared with the control grou

关 键 词:骨关节炎 尿 生物标志物 代谢通路 大鼠 

分 类 号:R684.3[医药卫生—骨科学]

 

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