婴儿巨细胞病毒肝炎不同中医证型的尿液代谢组学研究
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摘要
目的探讨婴儿巨细胞病毒肝炎不同证型的尿液代谢组学特征。方法筛选84例婴儿巨细胞病毒肝炎患儿分为湿热内蕴证(39例)、脾虚湿困证(28例)、气滞血瘀证(17例),另选健康对照组39名。采用气相色谱及质谱联用(GC-MS)技术对尿液样本进行代谢组学检测,经主成分分析寻找各证型的差异性代谢物。结果生化指标分析显示:湿热内蕴证与脾虚湿困证的总胆红素、结合胆红素及碱性磷酸酶水平存在差异(P <0. 05);湿热内蕴证与气滞血瘀证的天门冬氨酸氨基转移酶、总胆红素、结合胆红素、总胆汁酸水平及凝血酶原时间存在差异(P <0. 05);脾虚湿困证与气滞血瘀证的天门冬氨酸氨基转移酶、总胆红素、结合胆红素、总胆汁酸、碱性磷酸酶水平及凝血酶原时间存在差异(P <0. 05)。代谢组学研究显示:各证型在OPLS-DA图上区分明显,各证型间差异性代谢物涉及多种氨基酸代谢、能量代谢及肠道菌群相关代谢物紊乱。结论婴儿巨细胞病毒肝炎湿热内蕴证、脾虚湿困证及气滞血瘀证存在各自的尿液代谢组学特征。
Objective To investigate the urinary metabolomic characteristics of different Chinese medicine( CM)syndromes in infantile human cytomegalovirus hepatitis. Methods Totally 84 infantile human cytomegalovirus hepatitis patients were screened and assigned to damp-heat syndrome( 39 cases),Pi-deficiency with dampness encumbrance syndrome( 28 cases),Qi stagnation and blood stasis syndrome( 17 cases). Another 39 cases of normal control were collected at the same time. A non-targeted gas chromatography-mass spectrometry( GC-MS) metabolomics method was used in conjunction with orthogonal partial least squares discriminant analysis( OPLS-DA) to explore the differential metabolites and pathways of the three CM syndromes. Results In clinical index analysis,damp-heat syndrome and Pi-deficiency with dampness encumbrance syndrome differ in total bilirubin( TBIL),direct bilirubin( DBIL) and alkaline phosphatase( ALP,P < 0. 05).Damp-heat syndrome and Qi stagnation and blood stasis syndrome differ in aspartate aminotransferase( AST),TBIL,DBIL,total bile acid( TBA) and prothrombin time( PT,P < 0. 05). Pi-deficiency with dampness encumbrance syndrome and Qi stagnation and blood stasis syndrome differ in AST,TBIL,DBIL,TBA,ALP and PT(P < 0. 05). In metabolomic study,the OPLS-DA score plots revealed clear differentiation among the three CM syndromes. The differential metabolites between the three CM syndromes involve a variety of amino acid metabolism,energy metabolism and intestinal bacterial metabolism disorders. Conclusion Three CM syndromes of infantile human cytomegalovirus hepatitis have specific urinary metabolomic profiles,which indicated that different CM syndromes have their specific biological basis.
Objective To investigate the urinary metabolomic characteristics of different Chinese medicine( CM)syndromes in infantile human cytomegalovirus hepatitis. Methods Totally 84 infantile human cytomegalovirus hepatitis patients were screened and assigned to damp-heat syndrome( 39 cases),Pi-deficiency with dampness encumbrance syndrome( 28 cases),Qi stagnation and blood stasis syndrome( 17 cases). Another 39 cases of normal control were collected at the same time. A non-targeted gas chromatography-mass spectrometry( GC-MS) metabolomics method was used in conjunction with orthogonal partial least squares discriminant analysis( OPLS-DA) to explore the differential metabolites and pathways of the three CM syndromes. Results In clinical index analysis,damp-heat syndrome and Pi-deficiency with dampness encumbrance syndrome differ in total bilirubin( TBIL),direct bilirubin( DBIL) and alkaline phosphatase( ALP,P < 0. 05).Damp-heat syndrome and Qi stagnation and blood stasis syndrome differ in aspartate aminotransferase( AST),TBIL,DBIL,total bile acid( TBA) and prothrombin time( PT,P < 0. 05). Pi-deficiency with dampness encumbrance syndrome and Qi stagnation and blood stasis syndrome differ in AST,TBIL,DBIL,TBA,ALP and PT(P < 0. 05). In metabolomic study,the OPLS-DA score plots revealed clear differentiation among the three CM syndromes. The differential metabolites between the three CM syndromes involve a variety of amino acid metabolism,energy metabolism and intestinal bacterial metabolism disorders. Conclusion Three CM syndromes of infantile human cytomegalovirus hepatitis have specific urinary metabolomic profiles,which indicated that different CM syndromes have their specific biological basis.
引文
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[15]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[J].中华中医药杂志,2017,32(3):1246-1250.
[16]Li WW,Shan JJ,Lin LL,et al.Disturbance in plasma metabolic profile in different types of human cytomegalovirus-induced liver injury in infants[J].Sci Rep,2017,7(1):1-10.
[17]Li WW,Yang Y,Dai QG,et al.Non-invasive urinary metabolomic profiles discriminate biliary atresia from infantile hepatitis syndrome[J].Metabolomics,2018,14(7):89-90.
[18]廖圣银,曾俊,王爱瑶,等.慢性胃炎脾胃湿热证大鼠胃黏膜蛋白质组与三仁汤治疗的实验研究[J].中国中西医结合杂志,2013,33(1):76-80.
[19]Dai J,Sun SJ,Cao JM,et al.Similar connotation in chronic hepatitis B and nonalcoholic fatty liver patients with dampnessheat syndrome[J].Evid-based Complement Alternat Med,2013(2):1-12.
[20]邵铁娟,李海昌,谢志军,等.基于脾主运化理论探讨脾虚湿困与肠道菌群紊乱的关系[J].中华中医药杂志,2014(12):3762-3765.
[21]朱明丹,杜武勋,魏聪聪,等.不同证型冠心病患者的血浆代谢组学研究[J].中医杂志,2013,54(17):1489-1493.
[2]Patti G J,Yanes O,Siuzdak G.Metabolomics:the apogee of the omic triology[J].Nat Rev Mol Cell Biol,2011,13(4):263.
[3]汪受传,杜丽娜,单进军,等.应用代谢组学探讨小儿病毒性肺炎中医证候标准化的研究思路[J].中医儿科杂志,2013,9(1):1-3.
[4]Boppana SB,Ross SA,Fowler KB.Congenital cytomegalovirus infection:clinical outcome[J].Clin Infect Dis,2013,57(4):178-181.
[5]Dreher AM,Arora N,Fowler KB,et al.Spectrum of disease and outcome in children with symptomatic congenital cytomegalovirus infection[J].J Pediatr,2014,164(4):855-859.
[6]段泓宇,喻韬,万朝敏.巨细胞病毒感染诊断及治疗进展[J].中华妇幼临床医学杂志,2010,6(1):68-71.
[7]Tezer H,Se9meer G,Kara A,et al.Cytomegalovirus hepatitis and ganciclovir treatment in immunocompetent children[J].Turk J Pediatr,2008,50(3):228-234.
[8]Biron KK.Antiviral drugs for cytomegalovirus diseases[J].Antiviral Res,2006,71(2-3):154-163.
[9]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[J].辽宁中医杂志,2015,42(12):2458-2461.
[10]李维薇,杨燕,谢辉辉,等.中西医结合治疗婴儿巨细胞病毒肝炎临床疗效及安全性Meta分析[J].中国实验方剂学杂志,2016,22(20):178-182.
[11]胡亚美,江载芳,申昆玲,等主编.诸福棠实用儿科学[M].第8版.北京:人民卫生出版社,2015:910-915.
[12]中华中医药学会.中医儿科常见病诊疗指南[M].北京:中国中医药出版社,2012:163-166.
[13]Wang X,Zhang A,Han Y,et al.Urine metabolomics analysis for biomarker discovery and detection of jaundice syndrome in patients with liver disease[J].Mol Cell Proteomics,2012,11(8):370-380.
[14]郭孜,王文玉,戴建业,等.乙肝后肝硬化证候的尿代谢组学研究[J].世界科学技术-中医药现代化,2012,14(1):1282-1287.
[15]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[J].中华中医药杂志,2017,32(3):1246-1250.
[16]Li WW,Shan JJ,Lin LL,et al.Disturbance in plasma metabolic profile in different types of human cytomegalovirus-induced liver injury in infants[J].Sci Rep,2017,7(1):1-10.
[17]Li WW,Yang Y,Dai QG,et al.Non-invasive urinary metabolomic profiles discriminate biliary atresia from infantile hepatitis syndrome[J].Metabolomics,2018,14(7):89-90.
[18]廖圣银,曾俊,王爱瑶,等.慢性胃炎脾胃湿热证大鼠胃黏膜蛋白质组与三仁汤治疗的实验研究[J].中国中西医结合杂志,2013,33(1):76-80.
[19]Dai J,Sun SJ,Cao JM,et al.Similar connotation in chronic hepatitis B and nonalcoholic fatty liver patients with dampnessheat syndrome[J].Evid-based Complement Alternat Med,2013(2):1-12.
[20]邵铁娟,李海昌,谢志军,等.基于脾主运化理论探讨脾虚湿困与肠道菌群紊乱的关系[J].中华中医药杂志,2014(12):3762-3765.
[21]朱明丹,杜武勋,魏聪聪,等.不同证型冠心病患者的血浆代谢组学研究[J].中医杂志,2013,54(17):1489-1493.