法医学杂志

法医学杂志 ›› 2018, Vol. 34 ›› Issue (3): 228-232.DOI: 10.12116/j.issn.1004-5619.2018.03.002

• 论著 • 上一篇    下一篇

基于模式识别方法研究深静脉血栓形成大鼠尿液代谢物谱

曹  洁1，吕晓革2，李  宇3，靳茜茜1，储晓云1，王英元1，孙俊红1   

  1. 1. 山西医科大学法医学院，山西 太原 030001； 2. 重庆市公安局刑警总队，重庆 401147； 3. 山西省肿瘤医院，山西 太原 030009
  • 发布日期:2018-06-25 出版日期:2018-06-28
  • 通讯作者: 孙俊红，男，博士，教授，主要从事损伤病理学和猝死病理学研究；E-mail：sunjunhong146@163.com 王英元，男，教授，博士研究生导师，主要从事法医病理学研究；E-mail：wyy580218@163.com
  • 作者简介:曹洁（1983—），女，博士，讲师，主要从事法医毒物及病理学研究；E-mail：jie.cao@sxmu.edu.cn
  • 基金资助:
    国家自然科学基金资助项目（81470088）

Study on Urinary Metabolic Profile in Rats with Deep Venous Thrombosis Based on Pattern Recognition

CAO Jie1, Lv Xiao-ge2, LI Yu3, JIN Qian-qian1, CHU Xiao-yun1, WANG Ying-yuan1, SUN Jun-hong1CAO Jie1, LU Xiao-ge2, LI Yu3, JIN Qian-qian1, CHU Xiao-yun1, WANG Ying-yuan1, SUN Jun-hong1   

  1. 1. School of Forensic Medicine, Shanxi Medical University, Taiyuan 030001, China; 2. Criminal Police Department of Chongqing Public Security Bureau, Chongqing 401147, China; 3. Shanxi Tumour Hospital, Taiyuan 030009, China
  • Online:2018-06-25 Published:2018-06-28

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摘要： 目的 采用代谢组学技术研究深静脉血栓形成（deep venous thrombosis，DVT）大鼠尿液中代谢物谱，筛选出可用于DVT诊断和法医学鉴定的小分子生物标志物。 方法 建立下腔静脉完全结扎DVT大鼠模型，分为模型组、假手术组和对照组，每组各10只。模型组和假手术组大鼠在建模后48 h于代谢笼中收集24 h尿液，同时对照组收集24 h尿液。核磁共振检测其代谢物谱，SIMCA-P 14.1软件进行模式识别，通过正交偏最小二乘法-判别分析（orthogonal PLS-DA，OPLS-DA）模型中的变量权重重要性排序（variable importance in projection，VIP）值结合Mann-Whitney U检验，寻找尿液中差异代谢物。 结果 模型组、假手术组和对照组大鼠尿液的代谢轮廓呈现显著性差异。通过偏最小二乘法-判别分析（partial least squares method-discriminant analysis，PLS-DA）模型可以有效判别模型组、假手术组与对照组。与对照组大鼠相比，DVT大鼠尿液中亮氨酸、谷氨酰胺、肌酸、肌酐和蔗糖水平上调，3-羟基丁酸、乳酸、丙酮、α-酮戊二酸、柠檬酸和马尿酸水平下调。 结论 DVT大鼠尿液中的差异代谢物有望成为该疾病的候选生物标志物，该结果可为DVT的诊断、治疗和法医学鉴定提供研究基础。

关键词: 法医病理学, 代谢组学, 深静脉血栓形成, 核磁共振, 模式识别, 大鼠, 尿

Abstract: Objective To study the urinary metabolic profile in rats with deep venous thrombosis （DVT） based on metabolomics and to screen out small molecular biomarkers for the diagnosis and forensic identification of DVT. Methods Inferior vena cava of rats was ligated to construct DVT models. The rats were randomly divided into three groups： DVT, sham, and control groups, 10 in each group. The urine of DVT and sham rats was collected during 24 hours in the metabolic cage at 48 hours after operating, meanwhile, 24 hours urine was collected in control group. The metabolic profile was analyzed by nuclear magnetic resonance. SIMCA-P 14.1 software was used for pattern recognition. The variable importance in projection （VIP） value from orthogonal PLS-DA （OPLS-DA） model combined with Mann-Whitney U test were used to search the different metabolites in the urine. Results The metabolic profiles of urine from DVT, sham, and control groups had significant differences. The DVT, sham, and control groups could be distinguished by the partial least squares method-discriminant analysis （PLS-DA） model. Compared with the urine of the rats in control groups, the levels of leucine, glutamine, creatine, creatinine and sucrose in the urine of DVT rats were up-regulated, and the levels of 3-hydroxybutyrate, lactate, acetone, α-oxoglutarate, citrate and hippurate were down-regulated. Conclusion The different metabolites in the urine of DVT rats are expected to become its candidate biomarkers. The results can provide a research basis for the diagnosis, treatment and forensic identification of DVT.

Key words: forensic pathology, metabolomics, deep venous thrombosis, nuclear magnetic resonance, pattern recognition, rats, urine