首页 杂志概况 投稿须知 在线投稿 在线阅读 征订启事 广告服务 行业资讯 企业动态 资料中心  专访报道 会展信息 ENGLISH

引用本文:   彭琳秀, 谢彤, 单进军. 基于气相色谱-质谱联用的抗结核药致肾损伤代谢组学及谷胱甘肽治疗作用研究. 分析化学, 2020, 48(9): 1160-1168. doi:  10.19756/j.issn.0253-3820.191579 [复制]

Citation:   PENG Lin-Xiu , XIE Tong , SHAN Jin-Jun . Metabolomic Study of Kidney Injury Induced by Antitubercular Drugs and Therapeutic Effect of Glutathione Based on Gas Chromatography-Mass Spectrometry. Chinese Journal of Analytical Chemistry, 2020, 48(9): 1160-1168. doi: 10.19756/j.issn.0253-3820.191579 [复制]

基于气相色谱-质谱联用的抗结核药致肾损伤代谢组学及谷胱甘肽治疗作用研究

通讯作者:  单进军, jshan@njucm.edu.cn

收稿日期: 2019-10-29

基金项目: 本文系江苏省中药药效与安全性评价重点实验室资助项目(No.JKLPSE201505)和江苏省高校中药学优势学科建设工程项目(PAPD)资助

Metabolomic Study of Kidney Injury Induced by Antitubercular Drugs and Therapeutic Effect of Glutathione Based on Gas Chromatography-Mass Spectrometry

Corresponding author:  SHAN Jin-Jun , jshan@njucm.edu.cn

Received Date:  2019-10-29

Fund Project:  This work was supported by the Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica (No. JKLPSE201505) and the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

以异烟肼(INH,100 mg/(kg·d,ig))和RIF(RIF,100 mg/(kg·d,ig))为模型药物,连续灌胃14天诱导建立抗结核药大鼠肾损伤模型,以组织病理学、血清生化指标(尿素氮、肌酐)为考察对象,观察抗结核药物引起的肾损伤严重程度;采用基于气相色谱-质谱联用的代谢组学技术结合偏最小二乘法-判别分析等多维、单维统计方法探讨INH联用RIF对大鼠肾组织中内源性小分子化合物的代谢影响。采用对抗结核药物引起的组织细胞损伤具有保护作用的谷胱甘肽(GSH,250 mg/(kg·d,iv)对大鼠进行干预治疗,从代谢调控的角度阐明GSH发挥保肾的作用机制。组织病理学及血清生化结果显示,大鼠给予INH和RIF后,血清中尿素氮和肌酐水平显著升高(p<0.05),肾小管上皮中度空泡变性,提示肾组织出现损伤。代谢组学数据提示,结核药物联用导致了大鼠肾组织中酪氨酸、脯氨酸、尿苷、棕榈油酸等31个内源性物质代谢紊乱;主要导致了大鼠脂肪酸代谢、精氨酸和脯氨酸代谢异常。GSH能降低大鼠血清中尿素氮的水平(p<0.05),减轻大鼠肾小球系膜的增生情况;GSH能够通过调控肾组织中棕榈油酸、4-羟基丁酸、瓜氨酸、葡糖酸内酯、胍基乙酸和哌啶酸的代谢水平有效改善抗结核药物引起的大鼠肾组织损伤。

关键词:   抗结核药, 肾损伤, 谷胱甘肽, 代谢组学, 气相色谱-质谱联用
Key words:   Antitubercular drugs, Kidney injury, Glutathione, Metabolomics, Gas chromatography-mass spectrometry
[1]

Takii T, Seki K, Wakabayashi Y, Morishige Y, Sekizuka T, Yamashita A, Kato K, Uchimura K, Ohkado A, Keicho N, Mitarai S, Kuroda M, Kato S. Sci. Rep.,2019,9:12823

[2]

Nagel S, Streicher E M, Klopper M, Warren R M, Van Helden P D. Curr. Drug Metab.,2017,18(11):1030-1039

[3]

Maze M J, Paynter J, Chiu W, Hu R, Nisbet M, Lewis C. Int. J. Tubercul. Lung Disease,2016,20(7):955-960

[4]

Preziosi P. Curr. Drug Metab.,2007,8(8):839-851

[5]

Chiba S, Tsuchiya K, Sakashita H, Ito E, Inase N. Int. Med.,2013,52(21):2457-2460

[6]

Derungs A. Therapeutische Umschau. Revue Therapeutique,2015,72(11-12):717-727

[7]

Nicholson J K, Lindon J C, Holmes E. Xenobiotica,1999,29(11):1181-1189

[8]

Zhao Y Y, Tang D D, Chen H, Mao J R, Bai X, Cheng X H, Xiao X Y. Bioanalysis,2015,7(6):685-700

[9]

Xia D M, Lai X L, Wu K W, Zhou P Y, Li L, Guo Z Y, Xu S G. Biosci. Rep.,2019,39(11):BSR20192940

[10]

Kind T, Wohlgemuth G, Lee D Y, Lu Y, Palazoglu M, Shahbaz S, Fiehn O. Anal. Chem.,2009,81(24):10038-10048

[11]

Boczonadi V, Horvath R. Int. J. Biochem. Cell Biol.,2014,48:77-84

[12]

Ma X, Zhang Y, Jiang D, Yang Y, Wu G, Wu Z. J. Agric. Food Chem.,2019,67(17):4915-4922

[13]

da Silva R P, Nissim I, Brosnan M E, Brosnan J T. Am. J. Physiol. Endoc. Metab.,2009,296(2):E256-E261

计量
  • PDF下载量(7)
  • 文章访问量(56)
  • HTML全文浏览量(2)

目录

基于气相色谱-质谱联用的抗结核药致肾损伤代谢组学及谷胱甘肽治疗作用研究

彭琳秀, 谢彤, 单进军

Figures and Tables