摘要
目的:从尿液代谢组学层面探讨婴儿巨细胞病毒(HCMV)肝炎患儿湿热内蕴证、脾虚湿困证、气滞血瘀证的证候实质。方法:收集HCMV肝炎湿热内蕴证(44例)、脾虚湿困证(35例)、气滞血瘀证(43例)、正常对照组(40名)患儿,进行生化指标统计分析,同时采用超高效液相色谱-质谱联用技术,对患儿尿液样本进行代谢组学检测,经主成分分析寻找各证型的生物标志物。结果:在生化指标分析中,各证型组在丙氨酸氨基转移酶、门冬氨酸氨基转移酶、总胆红素、结合胆红素、总胆汁酸、谷氨酰转肽酶、碱性磷酸酶、乳酸脱氢酶及凝血酶原时间水平有显著差异。在代谢组学研究中,各证型组在正交偏最小二乘法-判别分析图上区分明显。各证型组均涉及氨基酸代谢紊乱。此外,各证型均有特征性生物标志物。结论:HCMV肝炎湿热内蕴证、脾虚湿困证及气滞血瘀证在生化指标和尿液代谢物水平均存在显著差异,表明不同中医证候有其生物学基础。
Objective: To study on the essence of infant cytomegalovirus hepatitis with syndrome of internal retention of damp-heat, syndrome of dampness stagnancy due to spleen deficiency and syndrome of qi stagnation and blood stasis based on urine metabolomics. Methods: Urine samples were collected from patients with syndrome of internal retention of damp-heat(44 cases), syndrome of dampness stagnancy due to spleen deficiency(35 cases), syndrome of qi stagnation and blood stasis(43 cases) and control group(40 cases), and the biochemical results of these patients were collected and analyzed. A non-targeted ultra high performance liquid chromatography-LTQ/orbitrap-mass spectrometry(UHPLC-LTQ/Orbitrap-MS) metabolomics method was used in conjunction with principle component analysis(PCA) to explore the differential metabolites of the three TCM syndromes. Results: In biochemical indicators analysis, three TCM syndromes differ in alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), direct bilirubin(DBIL), total bile acid(TBA), glutamyl transpeptidase(GGT), alkaline phosphatase(ALP), lactate dehydrogenase(LDH) and prothrombin time(PT). In metabolomic study, the orthogonal partial least squares discriminant analysis(OPLS-DA) score plots revealed clear differentiation among the three TCM syndromes. All the three TCM syndromes involve a variety of amino acid metabolism. In addition, every syndrome has its own characteristic biomarker. Conclusion: There are significant differences in biochemical indicators and urinary metabolomic profiles among the three TCM syndromes of infant cytomegalovirus hepatitis, which indicates that different TCM syndromes have their specific biological basis.
引文
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