PDF(Pubmed)
Abstract：
This study was to investigate the effects of ammonia and manganese in the metabolism of minimal hepatic encephalopathy (MHE). A total of 32 Sprague-Dawley rats were divided into four subgroups: chronic hyperammonemia (CHA), chronic hypermanganese (CHM), MHE and control group (CON). 1H-NMR-based metabolomics was used to detect the metabolic changes. Sparse projection to latent structures discriminant analysis was used for identifying and comparing the key metabolites. Significant elevated blood ammonia were shown in the CHA, CHM, and MHE rats. Significant elevated brain manganese (Mn) were shown in the CHM, and MHE rats, but not in the CHA rats. The concentrations of γ-amino butyric acid (GABA), lactate, alanine, glutamate, glutamine, threonine, and phosphocholine were significantly increased, and that of myo-inositol, taurine, leucine, isoleucine, arginine, and citrulline were significantly decreased in the MHE rats. Of all these 13 key metabolites, 10 of them were affected by ammonia (including lactate, alanine, glutamate, glutamine, myo-inositol, taurine, leucine, isoleucine, arginine, and citrulline) and 5 of them were affected by manganese (including GABA, lactate, myo-inositol, taurine, and leucine). Enrichment analysis indicated that abnormal metabolism of glutamine and TCA circle in MHE might be affected by the ammonia, and abnormal metabolism of GABA might be affected by the Mn, and abnormal metabolism of glycolysis and branched chain amino acids metabolism might be affected by both ammonia and Mn. Both ammonia and Mn play roles in the abnormal metabolism of MHE. Chronic hypermanganese could lead to elevated blood ammonia. However, chronic hyperammonemia could not lead to brain Mn deposition.
摘要：
本研究旨在探讨氨和锰在轻微肝性脑病（MHE）代谢中的作用。将32只Sprague-Dawley大鼠分为四个亚组：慢性高氨血症（CHA），慢性高锰（CHM），MHE组和对照组(CON)。使用基于1H-NMR的代谢组学来检测代谢变化。对潜在结构的稀疏投影判别分析用于鉴定和比较关键代谢物。CHA显示血氨显著升高，CHM,还有老鼠。在CHM中显示出脑锰（Mn）显着升高，和MHE老鼠，但不是在CHA老鼠身上。γ-氨基丁酸（GABA）的浓度，乳酸，丙氨酸,谷氨酸,谷氨酰胺,苏氨酸,和磷酸胆碱显著增加，还有肌醇，牛磺酸,亮氨酸,异亮氨酸,精氨酸MHE大鼠的瓜氨酸水平明显下降。在所有这13种关键代谢物中，其中10例受到氨的影响(包括乳酸，丙氨酸,谷氨酸,谷氨酰胺,肌醇,牛磺酸,亮氨酸,异亮氨酸,精氨酸和瓜氨酸），其中5个受到锰（包括GABA，乳酸，肌醇,牛磺酸,和亮氨酸）。富集分析表明，MHE中谷氨酰胺和TCA环的异常代谢可能受氨的影响，GABA的异常代谢可能受Mn的影响，糖酵解和支链氨基酸代谢异常可能受氨和锰的影响。氨和锰在MHE的异常代谢中起作用。慢性高锰会导致血氨升高。然而,慢性高氨血症不会导致脑锰沉积。
