组学技术在肝脏疾病证本质领域的研究进展
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摘要
组学技术可全面研究机体在疾病状态下体内基因表达、蛋白调控及代谢紊乱情况,其研究方法和中医学的整体观念相符合,是研究证候微观标准的先进方法。组学技术可作为肝脏疾病证本质研究的科学手段。文章通过对近十年组学技术用于肝脏疾病证本质研究的相关文献进行梳理,以乙型病毒性肝炎、肝硬化及肝癌等肝脏疾病为例,介绍了肝病领域已经发现的一系列证候相关生物标志物。但目前研究也存在纳入标准不统一、将证候实质局限总结为单一层面(如基因、蛋白及代谢物)的紊乱等问题。多组学的联用及构建基因-蛋白-代谢物-证候系统将有助于构建精确的辨证体系,揭示中医证候的生物学本质。
Omics technology can comprehensively study the in vivo gene regulation, protein regulation and metabolic disorder under the condition of diseases, and its research method is consistent with the holism of traditional Chinese medicine(TCM). Omics technology is an advanced method to study the microscopic standard of TCM syndrome. Therefore, omics technology can be used as a scientific method to explore the essence of the TCM syndrome of liver diseases. This paper reviewed the related literature about the application of omics technology in the study of the essence of the TCM syndrome of liver diseases in recent ten years. Taking liver diseases such as hepatitis B, cirrhosis, liver cancer, and so on as examples, this review introduced a series of biomarkers related to TCM syndromes found in liver diseases. However, there were still some problems in the current research, such as inconsistent inclusion criteria and summarizing the essence of TCM syndrome in a single level(such as genes, proteins, and metabolites) of the disorder. The combination of multiple omics technology and the construction of gene-proteinmetabolite-syndrome system will help to construct an accurate TCM syndrome differentiation system and reveal the biological essence of TCM syndrome.
Omics technology can comprehensively study the in vivo gene regulation, protein regulation and metabolic disorder under the condition of diseases, and its research method is consistent with the holism of traditional Chinese medicine(TCM). Omics technology is an advanced method to study the microscopic standard of TCM syndrome. Therefore, omics technology can be used as a scientific method to explore the essence of the TCM syndrome of liver diseases. This paper reviewed the related literature about the application of omics technology in the study of the essence of the TCM syndrome of liver diseases in recent ten years. Taking liver diseases such as hepatitis B, cirrhosis, liver cancer, and so on as examples, this review introduced a series of biomarkers related to TCM syndromes found in liver diseases. However, there were still some problems in the current research, such as inconsistent inclusion criteria and summarizing the essence of TCM syndrome in a single level(such as genes, proteins, and metabolites) of the disorder. The combination of multiple omics technology and the construction of gene-proteinmetabolite-syndrome system will help to construct an accurate TCM syndrome differentiation system and reveal the biological essence of TCM syndrome.
引文
[1]王斌全,高伟,吴勇延.头颈肿瘤多组学研究进展.临床耳鼻咽喉头颈外科杂志,2017,31(23):1785-1788
[2]Patti G J,Yanes O,Siuzdak G.Metabolomics:the apogee of the omic triology.Nature Reviews Molecular Cell Biology,2013,13(4):263
[3]Zhang X,Fang A,Riley C P,et al.Multi-dimensional liquid chromatography in proteomics:a review.Analytica Chimica Acta,2010,664(2):101-113
[4]Tang H,Wang Y.Metabonomics:a revolution in progress.Progress in Biochemistry&Biophysics,2006,33(5):401-417
[5]Wang F S,Fan J G,Zhang Z,et al.The global burden of liver disease:the major impact of China.Hepatology,2014,60(6):2099
[6]李维薇,杨燕,贺丽丽,等.婴儿巨细胞病毒肝炎的中医药研究进展.辽宁中医杂志,2015,42(12):2458-2461
[7]王融冰.肝病的中医药治疗.临床肝胆病杂志,2015,31(1):2-6
[8]Trépo C,Chan H L,Lok A.Hepatitis B virus infection.Lancet,2007,12(3):160-167
[9]王嗣予,黄辉煌,徐若男,等.肝病患者死亡原因分析:1 890例报告.解放军医学杂志,2014,39(5):392-395
[10]Liu J,Zhang S,Wang Q,et al.Seroepidemiology of hepatitis B virus infection in 2 million men aged 21-49 years in rural China:A population-based,cross-sectional study.Lancet Infectious Diseases,2015,16(1):80
[11]刘友平,李波,张光海,等.慢性乙型肝炎湿热中阻证的血浆代谢组学.世界华人消化杂志,2014,22(1):107-113
[12]魏嵋,刘友平,郭芳宏,等.慢性乙型病毒性肝炎湿热中阻证血浆蛋白质组学分析.中国中西医结合杂志,2011,31(10):1341-1345
[13]党思捷,罗雪梅,苏悦,等.转录组学在慢性乙型肝炎湿热类证鉴别中的应用.中华中医药杂志,2017,32(4):1516-1519
[14]Song Y N,Zhang H,Guan Y,et al.Classification of traditional Chinese medicine syndromes in patients with chronic hepatitis B by SELDI-based proteinchip analysis.Evidence-Based Complementary and Alternative Medicine,2012,3(1):1-10
[15]王磊琼,段新科,董宝刚.慢性乙型病毒性肝炎中医虚证的蛋白质组学规律初探.光明中医,2012,27(3):458-459
[16]杨婵娟,刘宏伟,王丽春,等.慢性乙型肝炎肝郁脾虚证和脾胃湿热证患者的差异表达基因研究初探.中国中西医结合杂志,2012,32(8):1032-1037
[17]赵丽红,王天芳,薛晓琳,等.801例肝炎肝硬化患者常见病性类证候要素在代偿期及失代偿期的分布特点.北京中医药大学学报,2015,38(4):260-265
[18]周烨威,徐品初,成扬,等.肝硬化正虚血瘀证候与血清蛋白质组学所见.中国中西医结合杂志,2011,31(5):595-602
[19]呼雪庆,苏式兵.基于全基因组甲基化的乙肝后肝硬化典型证候生物学基础观察.中华中医药杂志,2016,31(5):1868-1873
[20]Lu Y Y,Chen Q L,Guan Y,et al.Study of ZHENG differentiation in hepatitis B-caused cirrhosis:a transcriptional profiling analysis.BMC Complementary and Alternative Medicine,2014,14(1):371
[21]Sun S,Dai J,Wang W,et al.Metabonomic evaluation of ZHENG differentiation and treatment by Fuzhenghuayu Tablet in hepatitisB-caused cirrhosis.Evidence-Based Complementray and Alternative Medicine,2012,16(1):4-7
[22]Guo Z,Yu S,Guan Y,et al.Molecular mechanisms of same TCM syndrome for different diseases and different TCM syndrome for same disease in chronic hepatitis B and liver cirrhosis.EvidenceBased Complementray and Alternative Medicine,2012,10(1):1-10
[23]黄亚丽,张静,戚秀中,等.基于代谢组学分析冠心病和肝硬化血瘀证“异病同治”的物质基础.现代中西医结合杂志,2017,26(19):2053-2056
[24]吕桂帅,陈磊,王红阳.我国肝癌研究的现状与前景.生命科学,2015,27(3):237-248
[25]翟笑枫,顾瞻,陈喆,等.559例原发性肝癌患者中医证候分布规律研究.中医杂志,2016,57(12):1053-1056
[26]史话跃,吴承玉,杨涛.927例原发性肝癌证素特征研究.世界科学技术-中医药现代化,2014,16(3):643-648
[27]陈群伟,黄雪强,杨根金,等.原发性肝癌阳虚证患者血清代谢组特征初步研究.中华中医药学刊,2012,30(3):526-529
[28]翁莉,杜鹃,何文婷,等.原发性肝癌肝肾阴虚证患者外周血单个核细胞的特征性差异基因.结合医学学报(英文),2012,10(4):406-415
[29]刘雅荣,李晶洁,吕书勤.基于核磁共振的脾虚湿盛证肝癌患者血浆代谢组学研究.世界科学技术-中医药现代化,2016,18(2):296-301
[30]潘志强,方肇勤,卢文丽,等.肝癌小鼠不同阶段有关证候肾上腺差异表达的基因分析.结合医学学报(英文),2008,6(8):843-851
[31]魏滨,呼雪庆,宋雅楠,等.大肠癌和肝癌术后“异病同证”的代谢组学研究.世界科学技术-中医药现代化,2016,18(9):1500-1506
[32]Wang X,Zhang A,Han Y,et al.Urine metabolomics analysis for biomarker discovery and detection of jaundice syndrome in patients with liver disease.Molecular&Cellular Proteomics Mcp,2012,11(8):370-380
[33]宋婧,马致洁,王伽伯,等.湿热发黄证之乙型肝炎病毒相关慢加急性肝衰竭不同分期的生物标志物筛查.北京中医药,2016,35(12):1105-1108
[34]马欣,顾宏图,赵瑜,等.不同证候的非酒精性脂肪肝合并肝损伤患者的血清代谢组学分析.中华中医药杂志,2017,32(3):1246-1250
[35]Li W W,Shan J J,Lin L L,et al.Disturbance in plasma metabolic profile in different types of human cytomegalovirus:Induced liver injury in infants.Sci Rep,2017,7(1):1-8
[36]李维薇,汪受传,单进军,等.基于UHPLC-MS的代谢组学技术研究婴儿巨细胞病毒肝炎湿热内蕴证.南京中医药大学学报,2019,35(1):39-46
[37]贺丽丽,汪受传,李维薇,等.婴儿巨细胞病毒肝炎脾虚湿困证的代谢组学研究.中华中医药杂志,2018,33(10):4347-4351
[38]龚燕冰,倪青,王永炎.中医证候研究的现代方法学述评(一)——中医证候数据挖掘技术.北京中医药大学学报,2006,29(12):797-801
[39]郭蕾,王永炎,张志斌.关于证候概念的诠释.北京中医药大学学报,2003,26(2):5-8
[40]王永炎.完善中医辨证方法体系的建议.中医杂志,2004,45(10):729-731
[41]陈健,陈启龙,苏式兵.中医药精准医疗的思考与探索.世界科学技术-中医药现代化,2016,18(4):557-562
[2]Patti G J,Yanes O,Siuzdak G.Metabolomics:the apogee of the omic triology.Nature Reviews Molecular Cell Biology,2013,13(4):263
[3]Zhang X,Fang A,Riley C P,et al.Multi-dimensional liquid chromatography in proteomics:a review.Analytica Chimica Acta,2010,664(2):101-113
[4]Tang H,Wang Y.Metabonomics:a revolution in progress.Progress in Biochemistry&Biophysics,2006,33(5):401-417
[5]Wang F S,Fan J G,Zhang Z,et al.The global burden of liver disease:the major impact of China.Hepatology,2014,60(6):2099
[6]李维薇,杨燕,贺丽丽,等.婴儿巨细胞病毒肝炎的中医药研究进展.辽宁中医杂志,2015,42(12):2458-2461
[7]王融冰.肝病的中医药治疗.临床肝胆病杂志,2015,31(1):2-6
[8]Trépo C,Chan H L,Lok A.Hepatitis B virus infection.Lancet,2007,12(3):160-167
[9]王嗣予,黄辉煌,徐若男,等.肝病患者死亡原因分析:1 890例报告.解放军医学杂志,2014,39(5):392-395
[10]Liu J,Zhang S,Wang Q,et al.Seroepidemiology of hepatitis B virus infection in 2 million men aged 21-49 years in rural China:A population-based,cross-sectional study.Lancet Infectious Diseases,2015,16(1):80
[11]刘友平,李波,张光海,等.慢性乙型肝炎湿热中阻证的血浆代谢组学.世界华人消化杂志,2014,22(1):107-113
[12]魏嵋,刘友平,郭芳宏,等.慢性乙型病毒性肝炎湿热中阻证血浆蛋白质组学分析.中国中西医结合杂志,2011,31(10):1341-1345
[13]党思捷,罗雪梅,苏悦,等.转录组学在慢性乙型肝炎湿热类证鉴别中的应用.中华中医药杂志,2017,32(4):1516-1519
[14]Song Y N,Zhang H,Guan Y,et al.Classification of traditional Chinese medicine syndromes in patients with chronic hepatitis B by SELDI-based proteinchip analysis.Evidence-Based Complementary and Alternative Medicine,2012,3(1):1-10
[15]王磊琼,段新科,董宝刚.慢性乙型病毒性肝炎中医虚证的蛋白质组学规律初探.光明中医,2012,27(3):458-459
[16]杨婵娟,刘宏伟,王丽春,等.慢性乙型肝炎肝郁脾虚证和脾胃湿热证患者的差异表达基因研究初探.中国中西医结合杂志,2012,32(8):1032-1037
[17]赵丽红,王天芳,薛晓琳,等.801例肝炎肝硬化患者常见病性类证候要素在代偿期及失代偿期的分布特点.北京中医药大学学报,2015,38(4):260-265
[18]周烨威,徐品初,成扬,等.肝硬化正虚血瘀证候与血清蛋白质组学所见.中国中西医结合杂志,2011,31(5):595-602
[19]呼雪庆,苏式兵.基于全基因组甲基化的乙肝后肝硬化典型证候生物学基础观察.中华中医药杂志,2016,31(5):1868-1873
[20]Lu Y Y,Chen Q L,Guan Y,et al.Study of ZHENG differentiation in hepatitis B-caused cirrhosis:a transcriptional profiling analysis.BMC Complementary and Alternative Medicine,2014,14(1):371
[21]Sun S,Dai J,Wang W,et al.Metabonomic evaluation of ZHENG differentiation and treatment by Fuzhenghuayu Tablet in hepatitisB-caused cirrhosis.Evidence-Based Complementray and Alternative Medicine,2012,16(1):4-7
[22]Guo Z,Yu S,Guan Y,et al.Molecular mechanisms of same TCM syndrome for different diseases and different TCM syndrome for same disease in chronic hepatitis B and liver cirrhosis.EvidenceBased Complementray and Alternative Medicine,2012,10(1):1-10
[23]黄亚丽,张静,戚秀中,等.基于代谢组学分析冠心病和肝硬化血瘀证“异病同治”的物质基础.现代中西医结合杂志,2017,26(19):2053-2056
[24]吕桂帅,陈磊,王红阳.我国肝癌研究的现状与前景.生命科学,2015,27(3):237-248
[25]翟笑枫,顾瞻,陈喆,等.559例原发性肝癌患者中医证候分布规律研究.中医杂志,2016,57(12):1053-1056
[26]史话跃,吴承玉,杨涛.927例原发性肝癌证素特征研究.世界科学技术-中医药现代化,2014,16(3):643-648
[27]陈群伟,黄雪强,杨根金,等.原发性肝癌阳虚证患者血清代谢组特征初步研究.中华中医药学刊,2012,30(3):526-529
[28]翁莉,杜鹃,何文婷,等.原发性肝癌肝肾阴虚证患者外周血单个核细胞的特征性差异基因.结合医学学报(英文),2012,10(4):406-415
[29]刘雅荣,李晶洁,吕书勤.基于核磁共振的脾虚湿盛证肝癌患者血浆代谢组学研究.世界科学技术-中医药现代化,2016,18(2):296-301
[30]潘志强,方肇勤,卢文丽,等.肝癌小鼠不同阶段有关证候肾上腺差异表达的基因分析.结合医学学报(英文),2008,6(8):843-851
[31]魏滨,呼雪庆,宋雅楠,等.大肠癌和肝癌术后“异病同证”的代谢组学研究.世界科学技术-中医药现代化,2016,18(9):1500-1506
[32]Wang X,Zhang A,Han Y,et al.Urine metabolomics analysis for biomarker discovery and detection of jaundice syndrome in patients with liver disease.Molecular&Cellular Proteomics Mcp,2012,11(8):370-380
[33]宋婧,马致洁,王伽伯,等.湿热发黄证之乙型肝炎病毒相关慢加急性肝衰竭不同分期的生物标志物筛查.北京中医药,2016,35(12):1105-1108
[34]马欣,顾宏图,赵瑜,等.不同证候的非酒精性脂肪肝合并肝损伤患者的血清代谢组学分析.中华中医药杂志,2017,32(3):1246-1250
[35]Li W W,Shan J J,Lin L L,et al.Disturbance in plasma metabolic profile in different types of human cytomegalovirus:Induced liver injury in infants.Sci Rep,2017,7(1):1-8
[36]李维薇,汪受传,单进军,等.基于UHPLC-MS的代谢组学技术研究婴儿巨细胞病毒肝炎湿热内蕴证.南京中医药大学学报,2019,35(1):39-46
[37]贺丽丽,汪受传,李维薇,等.婴儿巨细胞病毒肝炎脾虚湿困证的代谢组学研究.中华中医药杂志,2018,33(10):4347-4351
[38]龚燕冰,倪青,王永炎.中医证候研究的现代方法学述评(一)——中医证候数据挖掘技术.北京中医药大学学报,2006,29(12):797-801
[39]郭蕾,王永炎,张志斌.关于证候概念的诠释.北京中医药大学学报,2003,26(2):5-8
[40]王永炎.完善中医辨证方法体系的建议.中医杂志,2004,45(10):729-731
[41]陈健,陈启龙,苏式兵.中医药精准医疗的思考与探索.世界科学技术-中医药现代化,2016,18(4):557-562