蛋白质组学及其在法医病理学中的应用
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摘要
蛋白质组学已成为现代生命科学领域中的热点之一,其应用前景已在临床医学研究中得到印证,如发现新的疾病生物标志物、鉴定疾病相关蛋白质、开发新的药物靶点等,但在法医学领域尤其是法医病理学领域尚处于探索阶段。本文从研究技术以及国内外学者将蛋白质组学技术应用于法医病理学的研究进展进行综述,以期为法医病理学的研究和应用提供新思路。
Proteomics has become one of the hot topics in modern life sciences. Its application prospects have been confirmed in clinical medical research, such as the discovery of new disease biomarkers, identification of disease-related proteins, and development of new drug targets. However, in the field of forensic science, especially in forensic pathology, it is still in the stage of exploration. This paper reviews the research techniques and the use of proteomics in forensic pathology in domestic and foreign scholars, in order to provide new ideas for the research and application of forensic pathology.
Proteomics has become one of the hot topics in modern life sciences. Its application prospects have been confirmed in clinical medical research, such as the discovery of new disease biomarkers, identification of disease-related proteins, and development of new drug targets. However, in the field of forensic science, especially in forensic pathology, it is still in the stage of exploration. This paper reviews the research techniques and the use of proteomics in forensic pathology in domestic and foreign scholars, in order to provide new ideas for the research and application of forensic pathology.
引文
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[3]丛斌.法医病理学[M].5版.北京:人民卫生出版社,2016.
[4]SOLTYS D T,PEREIRA C P,ISHIBE G N,et al.Effects of post mortem interval and gender in DNAbase excision repair activities in rat brains[J].Mutat Res,2015,776:48-53.
[5]MA J,PAN H,ZENG Y,et al.Exploration of the R code-based mathematical model for PMI estimation using profiling of RNA degradation in rat brain tissue at different temperatures[J].Forensic Sci Med Pathol,2015,11(4):530-537.
[6]LV Y H,MA K J,ZHANG H,et al.A time course study demonstrating mRNA,microRNA,18S rRNA,and U6 snRNA changes to estimate PMI in deceased rat’s spleen[J].J Forensic Sci,2014,59(5):1286-1294.
[7]ZENG Y,LV Y,TAO L,et al.G6PC3,ALDOAand CS induction accompanies mir-122 down-regulation in the mechanical asphyxia and can serve as hypoxia biomarkers[J].Oncotarget,2016,7(46):74526-74536.
[8]任磊,朱素敏,唐任宽,等.神经源性休克死亡家兔心肌组织差异蛋白分析[J].激光杂志,2011,32(1):87-89.
[9]KIKUCHI T,HASSANEIN M,AMANN J M,et al.In-depth proteomic analysis of nonsmall cell lung cancer to discover molecular targets and candidate biomarkers[J].Mol Cell Proteomics,2012,11(10):916-932.
[10]KRIEG R C,PAWELETZ C P,LIOTTA L A,et al.Clinical proteomics for cancer biomarker discovery and therapeutic targeting[J].Technol Cancer Res Treat,2002,1(4):263-272.
[11]刘宁国,陈忆九.MALDI-TOF-MS成像技术及其在法医损伤标志物筛选中的应用[J].法医学杂志,2014,30(5):367-370.
[12]任冠恒,翁榕花,施妍,等.MALDI-TOF-IMS在蛋白质组学研究中的新进展[J].法医学杂志,2016,32(2):126-130.
[13]陈庆,白洁,张文芳.应用iTRAQ-LC-MS/MS方法筛选大鼠DAI后脑组织差异表达蛋白质[J].法医学杂志,2017,33(4):348-352.
[14]KLOSE J.Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues.Anovel approach to testing for induced point mutations in mammals[J].Humangenetik,1975,26(3):231-243.
[15]O’FARRELL P H.High resolution two-dimensional electrophoresis of proteins[J].J Biol Chem,1975,250(10):4007-4021.
[16]UNLU M,MORGAN M E,MINDEN J S.Difference gel electrophoresis:a single gel method for detecting changes in protein extracts[J].Electrophoresis,1997,18(11):2071-2077.
[17]TONGE R,SHAW J,MIDDLETON B,et al.Validation and development of fluorescence two-dimensional differential gel electrophoresis proteomics technology[J].Proteomics,2001,1(3):377-396.
[18]MELEADY P.Two-dimensional gel electrophoresis and 2D-DIGE[J].Methods Mol Biol,2018,1664:3-14.
[19]HERNáNDEZ C,GARCIA-RAMIREZ M,CO-LOME N,et al.Identification of new pathogenic candidates for diabetic macular edema using fluorescence-based difference gel electrophoresis analysis[J].Diabetes Metab Res Rev,2013,29(6):499-506.
[20]CHO A,NORMILE D.Nobel Prize in chemistry.Mastering macromolecules[J].Science,2002,298(5593):527-528.
[21]INTELICATO-YOUNG J,FOX A.Mass spectrometry and tandem mass spectrometry characterization of protein patterns,protein markers and whole proteomes for pathogenic bacteria[J].J Microbiol Methods,2013,92(3):381-386.
[22]杨海慧,李秀颖,刘宁.蛋白质质谱分析技术的研究进展[J].智库时代,2018(36):239-242.
[23]谢增瑞,吴春灵,程相华.用串联质谱法提高毒鼠强的检测灵敏度[J].刑事技术,2003(1):24-25.
[24]MARSHALL E.Hot property:biologists who compute[J].Science,1996,272(5269):1730-1732.
[25]刘银凤,张雷.生物信息学数据库在医学研究中的应用[J].中国病原生物学杂志,2014,9(10):961-962.
[26]National Center for Biotechnology Information.Gene Expression Omnibus[EB/OL].[2018-01-23].https://www.ncbi.nlm.nih.gov/geo/.
[27]ZHU H,SNYDER M.Protein chip technology[J].Curr Opin Chem Biol,2003,7(1):55-63.
[28]STOLL D,BACHMANN J,TEMPLIN M F,et al.Microarray technology:an increasing variety of screening tools for proteomic research[J].Drug Discovery Today:TARGETS,2004,3(1):24-31.
[29]NUERRULA Y,REXIATI M,LIU Q,et al.Differential expression and clinical significance of serum protein among patients with clear-cell renal cell carcinoma[J].Cancer Biomark,2015,15(4):485-491.
[30]SILLETTI E,BULT J H,STIEGER M.Effect of NaCl and sucrose tastants on protein composition of oral fluid analysed by SELDI-TOF-MS[J].Arch Oral Biol,2012,57(9):1200-1210.
[31]ZHAO L,GAO Y,YANG Y,et al.Serum proteomic profiling analysis of chronic arsenic exposure by using SELDI-TOF-MS technology[J].Toxicol Lett,2010,195(2-3):155-160.
[32]朱军宝,刘步平,张泓,等.应用蛋白芯片技术筛选针刺对脑缺血再灌注损伤大鼠的凋亡相关蛋白[J].中南医学科学杂志,2014(3):222-225.
[33]ROSS P L,HUANG Y N,MARCHESE J N,et al.Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents[J].Mol Cell Proteomics,2004,3(12):1154-1169.
[34]HERGENROEDER G,REDELL J B,MOORE AN,et al.Identification of serum biomarkers in brain-injured adults:potential for predicting elevated intracranial pressure[J].J Neurotrauma,2008,25(2):79-93.
[35]KIKUCHI K,KAWAHARA K I,BISWAS K K,et al.HMGB1:a new marker for estimation of the postmortem interval[J].Exp Ther Med,2010,1(1):109-111.
[36]PARMAR A K,MENON S K.Estimation of postmortem interval through albumin in CSF by simple dye binding method[J].Sci Justice,2015,55(6):388-393.
[37]齐麟,李伟.人微管蛋白抗体的制备及其用于死亡时间推断的价值[J].郑州大学学报(医学版),2015(6):857-860.
[38]HUNSUCKER S W,SOLOMON B,GAWRYLUKJ,et al.Assessment of post-mortem-induced changes to the mouse brain proteome[J].J Neurochem,2008,105(3):725-737.
[39]FOUNTOULAKIS M,HARDMEIER R,HOGERH,et al.Postmortem changes in the level of brain proteins[J].Exp Neurol,2001,167(1):86-94.
[40]KWAK J,KIM H K,KIM K,et al.Proteomic evaluation of biomarkers to determine the postmortem interval[J].Anal Lett,2017,50(1):207-218.
[41]TAVICHAKORNTRAKOOL R,PRASONGWATTA-NA V,SRIBOONLUE P,et al.Serial analyses of postmortem changes in human skeletal muscle:a case study of alterations in proteome profile,histology,electrolyte contents,water composition,and enzyme activity[J].Proteomics Clin Appl,2008,2(9):1255-1264.
[42]ZHANG P,ZHU S,LI Y,et al.Quantitative proteomics analysis to identify diffuse axonal injury biomarkers in rats using iTRAQ coupled LC-MS/MS[J].J Proteomics,2016,133:93-99.
[43]DAMMEIER S,NAHNSEN S,VEIT J,et al.Massspectrometry-based proteomics reveals organ-specific expression patterns to be used as forensic evidence[J].J Proteome Res,2016,15(1):182-192.
[44]ECKHARDT A,KULHAVA L,MIKSIK I,et al.Proteomic analysis of cardiac ventricles:baso-apical differences[J].Mol Cell Biochem,2018,445(1-2):211-219.
[45]LIN L,LI H,LIN H,et al.Application of iTRAQ-based quantitative proteomics approach to identify deregulated proteins associated with liver toxicity induced by polygonum multiflorum in rats[J].Cell Physiol Biochem,2017,43(5):2102-2116.
[46]VAHDATI H F,ABNOUS K,MEHRI S,et al.Proteomics and phosphoproteomics analysis of liver in male rats exposed to bisphenol A:mechanism of hepatotoxicity and biomarker discovery[J].Food Chem Toxicol,2018,112:26-38.
[2]晏群,刘文恩,唐银.从基因组学到蛋白质组学:科学的推动力[J].医学与哲学,2003,24(2):12-15.
[3]丛斌.法医病理学[M].5版.北京:人民卫生出版社,2016.
[4]SOLTYS D T,PEREIRA C P,ISHIBE G N,et al.Effects of post mortem interval and gender in DNAbase excision repair activities in rat brains[J].Mutat Res,2015,776:48-53.
[5]MA J,PAN H,ZENG Y,et al.Exploration of the R code-based mathematical model for PMI estimation using profiling of RNA degradation in rat brain tissue at different temperatures[J].Forensic Sci Med Pathol,2015,11(4):530-537.
[6]LV Y H,MA K J,ZHANG H,et al.A time course study demonstrating mRNA,microRNA,18S rRNA,and U6 snRNA changes to estimate PMI in deceased rat’s spleen[J].J Forensic Sci,2014,59(5):1286-1294.
[7]ZENG Y,LV Y,TAO L,et al.G6PC3,ALDOAand CS induction accompanies mir-122 down-regulation in the mechanical asphyxia and can serve as hypoxia biomarkers[J].Oncotarget,2016,7(46):74526-74536.
[8]任磊,朱素敏,唐任宽,等.神经源性休克死亡家兔心肌组织差异蛋白分析[J].激光杂志,2011,32(1):87-89.
[9]KIKUCHI T,HASSANEIN M,AMANN J M,et al.In-depth proteomic analysis of nonsmall cell lung cancer to discover molecular targets and candidate biomarkers[J].Mol Cell Proteomics,2012,11(10):916-932.
[10]KRIEG R C,PAWELETZ C P,LIOTTA L A,et al.Clinical proteomics for cancer biomarker discovery and therapeutic targeting[J].Technol Cancer Res Treat,2002,1(4):263-272.
[11]刘宁国,陈忆九.MALDI-TOF-MS成像技术及其在法医损伤标志物筛选中的应用[J].法医学杂志,2014,30(5):367-370.
[12]任冠恒,翁榕花,施妍,等.MALDI-TOF-IMS在蛋白质组学研究中的新进展[J].法医学杂志,2016,32(2):126-130.
[13]陈庆,白洁,张文芳.应用iTRAQ-LC-MS/MS方法筛选大鼠DAI后脑组织差异表达蛋白质[J].法医学杂志,2017,33(4):348-352.
[14]KLOSE J.Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues.Anovel approach to testing for induced point mutations in mammals[J].Humangenetik,1975,26(3):231-243.
[15]O’FARRELL P H.High resolution two-dimensional electrophoresis of proteins[J].J Biol Chem,1975,250(10):4007-4021.
[16]UNLU M,MORGAN M E,MINDEN J S.Difference gel electrophoresis:a single gel method for detecting changes in protein extracts[J].Electrophoresis,1997,18(11):2071-2077.
[17]TONGE R,SHAW J,MIDDLETON B,et al.Validation and development of fluorescence two-dimensional differential gel electrophoresis proteomics technology[J].Proteomics,2001,1(3):377-396.
[18]MELEADY P.Two-dimensional gel electrophoresis and 2D-DIGE[J].Methods Mol Biol,2018,1664:3-14.
[19]HERNáNDEZ C,GARCIA-RAMIREZ M,CO-LOME N,et al.Identification of new pathogenic candidates for diabetic macular edema using fluorescence-based difference gel electrophoresis analysis[J].Diabetes Metab Res Rev,2013,29(6):499-506.
[20]CHO A,NORMILE D.Nobel Prize in chemistry.Mastering macromolecules[J].Science,2002,298(5593):527-528.
[21]INTELICATO-YOUNG J,FOX A.Mass spectrometry and tandem mass spectrometry characterization of protein patterns,protein markers and whole proteomes for pathogenic bacteria[J].J Microbiol Methods,2013,92(3):381-386.
[22]杨海慧,李秀颖,刘宁.蛋白质质谱分析技术的研究进展[J].智库时代,2018(36):239-242.
[23]谢增瑞,吴春灵,程相华.用串联质谱法提高毒鼠强的检测灵敏度[J].刑事技术,2003(1):24-25.
[24]MARSHALL E.Hot property:biologists who compute[J].Science,1996,272(5269):1730-1732.
[25]刘银凤,张雷.生物信息学数据库在医学研究中的应用[J].中国病原生物学杂志,2014,9(10):961-962.
[26]National Center for Biotechnology Information.Gene Expression Omnibus[EB/OL].[2018-01-23].https://www.ncbi.nlm.nih.gov/geo/.
[27]ZHU H,SNYDER M.Protein chip technology[J].Curr Opin Chem Biol,2003,7(1):55-63.
[28]STOLL D,BACHMANN J,TEMPLIN M F,et al.Microarray technology:an increasing variety of screening tools for proteomic research[J].Drug Discovery Today:TARGETS,2004,3(1):24-31.
[29]NUERRULA Y,REXIATI M,LIU Q,et al.Differential expression and clinical significance of serum protein among patients with clear-cell renal cell carcinoma[J].Cancer Biomark,2015,15(4):485-491.
[30]SILLETTI E,BULT J H,STIEGER M.Effect of NaCl and sucrose tastants on protein composition of oral fluid analysed by SELDI-TOF-MS[J].Arch Oral Biol,2012,57(9):1200-1210.
[31]ZHAO L,GAO Y,YANG Y,et al.Serum proteomic profiling analysis of chronic arsenic exposure by using SELDI-TOF-MS technology[J].Toxicol Lett,2010,195(2-3):155-160.
[32]朱军宝,刘步平,张泓,等.应用蛋白芯片技术筛选针刺对脑缺血再灌注损伤大鼠的凋亡相关蛋白[J].中南医学科学杂志,2014(3):222-225.
[33]ROSS P L,HUANG Y N,MARCHESE J N,et al.Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents[J].Mol Cell Proteomics,2004,3(12):1154-1169.
[34]HERGENROEDER G,REDELL J B,MOORE AN,et al.Identification of serum biomarkers in brain-injured adults:potential for predicting elevated intracranial pressure[J].J Neurotrauma,2008,25(2):79-93.
[35]KIKUCHI K,KAWAHARA K I,BISWAS K K,et al.HMGB1:a new marker for estimation of the postmortem interval[J].Exp Ther Med,2010,1(1):109-111.
[36]PARMAR A K,MENON S K.Estimation of postmortem interval through albumin in CSF by simple dye binding method[J].Sci Justice,2015,55(6):388-393.
[37]齐麟,李伟.人微管蛋白抗体的制备及其用于死亡时间推断的价值[J].郑州大学学报(医学版),2015(6):857-860.
[38]HUNSUCKER S W,SOLOMON B,GAWRYLUKJ,et al.Assessment of post-mortem-induced changes to the mouse brain proteome[J].J Neurochem,2008,105(3):725-737.
[39]FOUNTOULAKIS M,HARDMEIER R,HOGERH,et al.Postmortem changes in the level of brain proteins[J].Exp Neurol,2001,167(1):86-94.
[40]KWAK J,KIM H K,KIM K,et al.Proteomic evaluation of biomarkers to determine the postmortem interval[J].Anal Lett,2017,50(1):207-218.
[41]TAVICHAKORNTRAKOOL R,PRASONGWATTA-NA V,SRIBOONLUE P,et al.Serial analyses of postmortem changes in human skeletal muscle:a case study of alterations in proteome profile,histology,electrolyte contents,water composition,and enzyme activity[J].Proteomics Clin Appl,2008,2(9):1255-1264.
[42]ZHANG P,ZHU S,LI Y,et al.Quantitative proteomics analysis to identify diffuse axonal injury biomarkers in rats using iTRAQ coupled LC-MS/MS[J].J Proteomics,2016,133:93-99.
[43]DAMMEIER S,NAHNSEN S,VEIT J,et al.Massspectrometry-based proteomics reveals organ-specific expression patterns to be used as forensic evidence[J].J Proteome Res,2016,15(1):182-192.
[44]ECKHARDT A,KULHAVA L,MIKSIK I,et al.Proteomic analysis of cardiac ventricles:baso-apical differences[J].Mol Cell Biochem,2018,445(1-2):211-219.
[45]LIN L,LI H,LIN H,et al.Application of iTRAQ-based quantitative proteomics approach to identify deregulated proteins associated with liver toxicity induced by polygonum multiflorum in rats[J].Cell Physiol Biochem,2017,43(5):2102-2116.
[46]VAHDATI H F,ABNOUS K,MEHRI S,et al.Proteomics and phosphoproteomics analysis of liver in male rats exposed to bisphenol A:mechanism of hepatotoxicity and biomarker discovery[J].Food Chem Toxicol,2018,112:26-38.