实验和临床肝纤维化都留下了代谢足迹,可以使用代谢组学方法来发现和定义。代谢组学将模式识别算法与分析化学相结合,特别是,1H和13C核磁共振波谱(NMR),气相色谱-质谱(GC-MS)和各种液相色谱-质谱(LC-MS)平台。通过这些方法中的每一种对肝纤维化的分析分别进行审查。令人惊讶的是,这三组中的每一组内的研究之间以及组间的研究之间几乎没有共识.通过NMR确定的代谢组学足迹(研究之间的两次或更多次命中)包括乳酸升高,醋酸盐,胆碱,3-羟基丁酸酯,葡萄糖,组氨酸,蛋氨酸,谷氨酰胺,苯丙氨酸,酪氨酸和柠檬酸盐。对于GC-MS,琥珀酸盐,富马酸盐,苹果酸,抗坏血酸,谷氨酸,甘氨酸,丝氨酸和,与NMR一致,谷氨酰胺,苯丙氨酸,描绘了酪氨酸和柠檬酸盐。对于LC-MS,只有β-胞嘧啶酸,色氨酸,酰基肉碱,对甲酚,缬氨酸和,与NMR一致,磷酸胆碱被鉴定。关于谷氨酰胺,肝纤维化的代谢组学足迹上调,苯丙氨酸,酪氨酸,柠檬酸盐和磷酸胆碱。几位研究人员采用中药(TCM)治疗来逆转实验性肝纤维化,并对可能具有纤维化活性的化学成分进行了评论。有人提出,使用这些中药成分的分子对接程序可能会导致肝纤维化的新疗法,影响全球至少二十分之一的人。目前还没有药物治疗。这篇深入的综述总结了代谢组学的相关文献及其在解决肝纤维化临床问题中的意义,肝硬化及其后遗症。
Both experimental and clinical liver fibrosis leave a metabolic footprint that can be uncovered and defined using metabolomic approaches. Metabolomics combines pattern recognition algorithms with analytical chemistry, in particular, 1H and 13C nuclear magnetic resonance spectroscopy (NMR), gas chromatography-mass spectrometry (GC-MS) and various liquid chromatography-mass spectrometry (LC-MS) platforms. The analysis of liver fibrosis by each of these methodologies is reviewed separately. Surprisingly, there was little general agreement between studies within each of these three groups and also between groups. The metabolomic footprint determined by NMR (two or more hits between studies) comprised elevated lactate, acetate, choline, 3-hydroxybutyrate, glucose, histidine, methionine, glutamine, phenylalanine, tyrosine and citrate. For GC-MS, succinate, fumarate, malate, ascorbate, glutamate, glycine, serine and, in agreement with NMR, glutamine, phenylalanine, tyrosine and citrate were delineated. For LC-MS, only β-muricholic acid, tryptophan, acylcarnitine, p-cresol, valine and, in agreement with NMR, phosphocholine were identified. The metabolomic footprint of liver fibrosis was upregulated as regards glutamine, phenylalanine, tyrosine, citrate and phosphocholine. Several investigators employed traditional Chinese medicine (TCM) treatments to reverse experimental liver fibrosis, and a commentary is given on the chemical constituents that may possess fibrolytic activity. It is proposed that molecular docking procedures using these TCM constituents may lead to novel therapies for liver fibrosis affecting at least one-in-twenty persons globally, for which there is currently no pharmaceutical cure. This in-depth review summarizes the relevant literature on metabolomics and its implications in addressing the clinical problem of liver fibrosis, cirrhosis and its sequelae.