留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

应中央军委要求,2022年9月起,《药学实践杂志》将更名为《药学实践与服务》,双月刊,正文96页;2023年1月起,拟出版月刊,正文64页,数据库收录情况与原《药学实践杂志》相同。欢迎作者踊跃投稿!

基于UPLC-Q-TOF/MS平台的结晶肾损伤小鼠的尿液代谢组学研究

王学雷 晁玉凡 高松燕 董昕 温晓飞

王学雷, 晁玉凡, 高松燕, 董昕, 温晓飞. 基于UPLC-Q-TOF/MS平台的结晶肾损伤小鼠的尿液代谢组学研究[J]. 药学实践与服务, 2019, 37(2): 126-134. doi: 10.3969/j.issn.1006-0111.2019.02.006
引用本文: 王学雷, 晁玉凡, 高松燕, 董昕, 温晓飞. 基于UPLC-Q-TOF/MS平台的结晶肾损伤小鼠的尿液代谢组学研究[J]. 药学实践与服务, 2019, 37(2): 126-134. doi: 10.3969/j.issn.1006-0111.2019.02.006
WANG Xuelei, CHAO Yufan, GAO Songyan, DONG Xin, WEN Xiaofei. Urinary metabolomics study on mice renal injury caused by calcium oxalate crystal based on UPLC-Q-TOF/MS platform[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(2): 126-134. doi: 10.3969/j.issn.1006-0111.2019.02.006
Citation: WANG Xuelei, CHAO Yufan, GAO Songyan, DONG Xin, WEN Xiaofei. Urinary metabolomics study on mice renal injury caused by calcium oxalate crystal based on UPLC-Q-TOF/MS platform[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(2): 126-134. doi: 10.3969/j.issn.1006-0111.2019.02.006

基于UPLC-Q-TOF/MS平台的结晶肾损伤小鼠的尿液代谢组学研究

doi: 10.3969/j.issn.1006-0111.2019.02.006
基金项目: 上海市浦东新区科技发展基金(PKJ2013-Y21);上海市科学技术委员会科研计划项目(15401900800)

Urinary metabolomics study on mice renal injury caused by calcium oxalate crystal based on UPLC-Q-TOF/MS platform

  • 摘要: 目的 通过研究草酸钙结石小鼠尿液中代谢物的变化,探究草酸钙结晶导致肾损伤的内在机制。 方法 以乙醛酸盐诱导的小鼠草酸钙结晶模型为对象,采用基于超高效液相-四极杆飞行时间串联质谱(UPLC-Q-TOF/MS)的代谢组学方法测定尿液中内源性代谢物的变化,并采用SIMCA-P进行多元统计分析,Metabo Analyst软件进行代谢物通路分析。 结果 与正常组相比,模型组小鼠的肾组织出现明显的钙盐沉积且血清中的肌酐和尿素氮含量异常升高,肾脏出现损伤;从尿液中筛选出尿酸、牛磺酸、苯丙氨酸等21个差异代谢物。 结论 通过代谢物通路分析,差异代谢物主要涉及氨基酸代谢、能量代谢、牛磺酸代谢、嘌呤代谢和VB6代谢,为进行结石疾病机制研究以及早期标志物的筛选提供了重要参考。
  • [1] XU H,ZISMAN A L,COE F L,et al.Kidney stones:an update on current pharmacological management and future directions[J].Expert Opin Pharmacother,2013,14(4):435-447.
    [2] ROMERO V,AKPINAR H,ASSIMOS D G.Kidney stones:a global picture of prevalence,incidence,and associated risk factors[J].Rev Urol,2010,12(2-3):e86-e96.
    [3] ZENG G H,MAI Z L,XIA S J,et al.Prevalence of kidney stones in China:an ultrasonography based cross-sectional study[J].BJU Int,2017,120:109-116.
    [4] SUTHERLAND J W,PARKS J H,COE F L.Recurrence after a single renal stone in a community practice[J].Miner Electrolyte Metab,1985,11(4):267-269.
    [5] RULE AD,BERGSTRALH E J,MELTON L J,et al.Kidney stones and the risk for chronic kidney disease[J].Clin J Am Soc Nephrol,2009,4(4):804-811.
    [6] EL-ZOGHBY Z M,LIESKE J C,FOLEY RN,et al.Urolithiasis and the risk of ESRD[J].Clin J Am Soc Nephrol,2012,7(9):1409-1415.
    [7] JOHNSON C M,WILSON D M,O'FALLON WM,et al.Renal stone epidemiology:a 25-year study in Rochester,Minnesota[J].Kidney Int,1979,16(5):624-631.
    [8] VERVAET B A,VERHULST A,DAUWE SE,et al.An active renal crystal clearance mechanism in rat and man[J].Kidney Int,2009,75(1):41-51.
    [9] KHAN S R.Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation:evidence from clinical and experimental investigations[J].J Urol,2013,189(3):803-811.
    [10] KHAN S R.Reactive oxygen species,inflammation and calcium oxalate nephrolithiasis[J].Transl Androl Urol,2014,3(3):256-276.
    [11] TASCA A.Metabolic syndrome and bariatric surgery in stone disease etiology[J].Curr Opin Urol,2011,21(2):129-133.
    [12] MOHAMMADJAFARI H,BARZIN M,SALEHIFAR E,et al.Etiologic and epidemiologic pattern of urolithiasis in north iran;review of 10-year findings[J].Iran J Pediatr,2014,24(1):69-74.
    [13] NICHOLSON J K,LINDON J C,HOLMES E.‘Metabonomics’:understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data[J].Xenobiotica,1999,29(11):1181-1189.
    [14] ROCHFORT S.Metabolomics reviewed:a new "omics" platform technology for systems biology and implications for natural products research[J].J Nat Prod,2005,68(12):1813-1820.
    [15] OKADA A,NOMURA S,HIGASHIBATA Y,et al.Successful formation of calcium oxalate crystal deposition in mouse kidney by intraabdominal glyoxylate injection[J].Urol Res,2007,35(2):89-99.
    [16] 高松燕.基于两种动物模型的结晶肾损伤形成机制及中药干预的代谢组学研究[D].上海:第二军医大学,2015.
    [17] CHAN E C,PASIKANTI K K,NICHOLSON J K.Global urinary metabolic profiling procedures using gas chromatography-mass spectrometry[J].Nat Protoc,2011,6(10):1483-1499.
    [18] SMILDE A K,van der WERF M J,BIJLSMA S,et al.Fusion of mass spectrometry-based metabolomics data[J].Anal Chem,2005,77(20):6729-6736.
    [19] TRYGG J,HOLMES E,LUNDSTEDT T.Chemometrics in metabonomics[J].J Proteome Res,2007,6(2):469-479.
    [20] WANG X,WANG H,ZHANG A,et al.Metabolomics study on the toxicity of aconite root and its processed products using ultraperformance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry coupled with pattern recognition approach and ingenuity pathways analysis[J].J Proteome Res,2012,11(2):1284-1301.
    [21] WISHART D S,JEWISON T,GUO A C,et al.HMDB 3.0 The Human Metabolome Database in 2013[J].Nucleic Acids Res,2013,41(Database issue):D801-D807.
    [22] IANG X,CHEN X,LIANG Q,et al.Metabonomic study of Chinese medicine Shuanglong formula as an effective treatment for myocardial infarction in rats[J].J Proteome Res,2011,10(2):790-799.
    [23] 高越.基于组学和网络药理学的养心氏片抗心衰作用机理研究[D].上海:第二军医大学,2016.
    [24] BOIRIE Y,ALBRIGHT R,BIGELOW M,et al.Impairment of phenylalanine conversion to tyrosine in end-stage renal disease causing tyrosine deficiency[J].Kidney Int,2004,66(2):591-596.
    [25] YOUNG B A,VON KORFF M,HECKBERT S R,et al.Association of major depression and mortality in Stage 5 diabetic chronic kidney disease[J].Gen Hosp Psychiatry,2010,32(2):119-124.
    [26] KERAI M D,WATERFIELD C J,KENYON S H,et al.Reversal of ethanol-induced hepatic steatosis and lipid peroxidation by taurine:a study in rats[J].Alcohol Alcohol,1999,34(4):529-541.
    [27] GUAN X,DEI-ANANE G,LIANG R,et al.Donor preconditioning with taurine protects kidney grafts from injury after experimental transplantation[J].J Surg Res,2008,146(1):127-134.
    [28] BADENHORST C P,van der SLUIS R,ERASMUS E,et al.Glycine conjugation:importance in metabolism,the role of glycine N-acyltransferase,and factors that influence interindividual variation[J].Expert Opin Drug Metab Toxicol,2013,9(9):1139-1153.
    [29] WILCOX B J,RITENOUR-RODGERS K J,ASSER A S,et al.N-acylglycine amidation:implications for the biosynthesis of fatty acid primary amides[J].Biochemistry,1999,38(11):3235-3245.
    [30] COSTA C G,GUERAND W S,STRUYS E A,et al.Quantitative analysis of urinary acylglycines for the diagnosis of beta-oxidation defects using GC-NCI-MS[J].J Pharm Biomed Anal,2000,21(6):1215-1224.
    [31] OMBRONE D,SALVATORE F,RUOPPOLO M.Quantitative liquid chromatography coupled with tandem mass spectrometry analysis of urinary acylglycines:application to the diagnosis of inborn errors of metabolism[J].Anal Biochem,2011,417(1):122-128.
    [32] LA MARCA G,RIZZO C.Analysis of organic acids and acylglycines for the diagnosis of related inborn errors of metabolism by GC-and HPLC-MS[J].Methods Mol Biol,2011,708:73-98.
    [33] KHAN S R.Reactive oxygen species,inflammation and calcium oxalate nephrolithiasis[J].Transl Androl Urol,2014,3(3):256-276.
    [34] KHAN S R.Renal tubular damage/dysfunction:key to the formation of kidney stones[J].Urol Res,2006,34(2):86-91.
    [35] KHAN S R.Role of renal epithelial cells in the initiation of calcium oxalate stones[J].Nephron Exp Nephrol,2004,98(2):e55-e60.
    [36] SCHEINMAN J I,VOZIYAN P A,BELMONT J M,et al.Pyridoxamine lowers oxalate excretion and kidney crystals in experimental hyperoxaluria:a potential therapy for primary hyperoxaluria[J].Urol Res,2005,33(5):368-371.
    [37] MITWALLI A,AYIOMAMITIS A,GRASS L,et al.Control of hyperoxaluria with large doses of pyridoxine in patients with kidney stones[J].Int Urol Nephrol,1988,20(4):353-359.
    [38] MILLINER D S,EICKHOLT J T,BERGSTRALH E J,et al.Results of long-term treatment with orthophosphate and pyridoxine in patients with primary hyperoxaluria[J].N Engl J Med,1994,331(23):1553-1558.
    [39] ORTIZ-ALVARADO O,MIYAOKA R,KRIEDBERG C,et al.Pyridoxine and dietary counseling for the management of idiopathic hyperoxaluria in stone-forming patients[J].Urology,2011,77(5):1054-1058.
    [40] DIJCKER J C,PLANTINGA E A,van BAAL J,et al.Influence of nutrition on feline calcium oxalate urolithiasis with emphasis on endogenous oxalate synthesis[J].Nutr Res Rev,2011,24(1):96-110.
    [41] JOHNSON R J,SANCHEZ-LOZADA L G,MAZZALI M,et al.What are the key arguments against uric acid as a true risk factor for hypertension[J].Hypertension,2013,61(5):948-951.
    [42] ROMERO F,PEREZ M,CHAVEZ M,et al.Effect of uric acid on gentamicin-induced nephrotoxicity in rats-role of matrix metalloproteinases 2 and 9[J].Basic Clin Pharmacol Toxicol,2009,105(6):416-424.
    [43] SHIMADA M,JOHNSON RJ,MAY W S Jr,et al.A novel role for uric acid in acute kidney injury associated with tumour lysis syndrome[J].Nephrol Dial Transplant,2009,24(10):2960-2964.
  • [1] 迟文雅, 袁艳, 李伟林, 吴茼妤, 俞媛.  负载骨髓间充质干细胞/白藜芦醇脂质体的水凝胶支架用于创伤性脑损伤治疗 . 药学实践与服务, 2024, 42(): 1-8. doi: 10.12206/j.issn.2097-2024.202406034
    [2] 杨嘉宁, 赵一颖, 肖伟.  七味脂肝方对非酒精性脂肪性肝炎动物模型的药效学评价 . 药学实践与服务, 2024, 42(9): 389-398. doi: 10.12206/j.issn.2097-2024.202404096
    [3] 宋雨桐, 夏德润, 顾珩, 唐少文, 易洪刚, 沃红梅.  帕博利珠单抗与铂类化疗方案在晚期非小细胞肺癌一线治疗中的药物经济学评价 . 药学实践与服务, 2024, 42(8): 334-340. doi: 10.12206/j.issn.2097-2024.202303023
    [4] 赖立勇, 夏天爽, 徐圣焱, 蒋益萍, 岳小强, 辛海量.  中药青蒿抗氧化活性的谱效关系研究 . 药学实践与服务, 2024, 42(5): 203-210, 216. doi: 10.12206/j.issn.2097-2024.202211012
    [5] 崔亚玲, 吴琼, 马良煜, 胡北, 姚东, 许子华.  肝素钠肌醇烟酸酯乳膏中肌醇烟酸酯皮肤药动学研究 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202404006
    [6] 舒飞, 孙蕊, 宋凯, 张元林, 闫家铭, 舒丽芯.  粉-液双室袋产品综合评估 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202312009
    [7] 冯志惠, 邓仪卿, 叶冰, 安培, 张宏, 张海军.  雀梅藤石油醚提取物诱导三阴性乳腺癌细胞凋亡的实验研究 . 药学实践与服务, 2024, 42(6): 253-259. doi: 10.12206/j.issn.2097-2024.202311055
    [8] 何静, 安晔, 张朝绅.  复方黑参滴丸与复方黑参丸药效学实验比较研究 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202404009
    [9] 毛智毅, 王筱燕, 陈晓颖, 汤逸斐.  度拉糖肽联合二甲双胍对肥胖型2型糖尿病患者机体代谢、体脂成分及血清脂肪因子的影响 . 药学实践与服务, 2024, 42(7): 305-309. doi: 10.12206/j.issn.2097-2024.202305032
    [10] 夏哲炜, 曾垣烨, 朱海菲, 李育, 陈啸飞.  核磁共振磷谱法测定磷酸氢钙咀嚼片中药物含量 . 药学实践与服务, 2024, 42(9): 399-401, 406. doi: 10.12206/j.issn.2097-2024.202404063
    [11] 张艺昕, 关欣怡, 王博宁, 闻俊, 洪战英.  二氢吡啶类钙离子拮抗药物手性分析及其立体选择性药动学研究进展 . 药学实践与服务, 2024, 42(8): 319-324. doi: 10.12206/j.issn.2097-2024.202308062
    [12] 孙丹倪, 黄勇, 张嘉宝, 王培.  代谢相关脂肪性肝病的无创诊断与药物治疗 . 药学实践与服务, 2024, 42(10): 411-418. doi: 10.12206/j.issn.2097-2024.202403049
  • 加载中
计量
  • 文章访问数:  3642
  • HTML全文浏览量:  527
  • PDF下载量:  421
  • 被引次数: 0
出版历程
  • 收稿日期:  2018-11-16
  • 修回日期:  2018-12-17

基于UPLC-Q-TOF/MS平台的结晶肾损伤小鼠的尿液代谢组学研究

doi: 10.3969/j.issn.1006-0111.2019.02.006
    基金项目:  上海市浦东新区科技发展基金(PKJ2013-Y21);上海市科学技术委员会科研计划项目(15401900800)

摘要: 目的 通过研究草酸钙结石小鼠尿液中代谢物的变化,探究草酸钙结晶导致肾损伤的内在机制。 方法 以乙醛酸盐诱导的小鼠草酸钙结晶模型为对象,采用基于超高效液相-四极杆飞行时间串联质谱(UPLC-Q-TOF/MS)的代谢组学方法测定尿液中内源性代谢物的变化,并采用SIMCA-P进行多元统计分析,Metabo Analyst软件进行代谢物通路分析。 结果 与正常组相比,模型组小鼠的肾组织出现明显的钙盐沉积且血清中的肌酐和尿素氮含量异常升高,肾脏出现损伤;从尿液中筛选出尿酸、牛磺酸、苯丙氨酸等21个差异代谢物。 结论 通过代谢物通路分析,差异代谢物主要涉及氨基酸代谢、能量代谢、牛磺酸代谢、嘌呤代谢和VB6代谢,为进行结石疾病机制研究以及早期标志物的筛选提供了重要参考。

English Abstract

王学雷, 晁玉凡, 高松燕, 董昕, 温晓飞. 基于UPLC-Q-TOF/MS平台的结晶肾损伤小鼠的尿液代谢组学研究[J]. 药学实践与服务, 2019, 37(2): 126-134. doi: 10.3969/j.issn.1006-0111.2019.02.006
引用本文: 王学雷, 晁玉凡, 高松燕, 董昕, 温晓飞. 基于UPLC-Q-TOF/MS平台的结晶肾损伤小鼠的尿液代谢组学研究[J]. 药学实践与服务, 2019, 37(2): 126-134. doi: 10.3969/j.issn.1006-0111.2019.02.006
WANG Xuelei, CHAO Yufan, GAO Songyan, DONG Xin, WEN Xiaofei. Urinary metabolomics study on mice renal injury caused by calcium oxalate crystal based on UPLC-Q-TOF/MS platform[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(2): 126-134. doi: 10.3969/j.issn.1006-0111.2019.02.006
Citation: WANG Xuelei, CHAO Yufan, GAO Songyan, DONG Xin, WEN Xiaofei. Urinary metabolomics study on mice renal injury caused by calcium oxalate crystal based on UPLC-Q-TOF/MS platform[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(2): 126-134. doi: 10.3969/j.issn.1006-0111.2019.02.006
参考文献 (43)

目录

    /

    返回文章
    返回