Guazzelli Pedro Arend, Fachim Felipe Dos Santos, Travassos Anderson Santos, Schaukoski Caroline Casagrande, Ferreira Pâmela Cristina Lukasewicz, Fontella Fernanda Uruth, de Bastiani Marco Antônio, de Assis Adriano Martimbianco, Souza Diogo Onofre
Graduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul-UFRGS, Porto Alegre 90035-003, Brazil.
Graduate Program in Pharmaceutical Sciences, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre 90610-000, Brazil.
Metabolites. 2025 Sep 8;15(9):598. doi: 10.3390/metabo15090598.
BACKGROUND/OBJECTIVES: Hepatic encephalopathy (HE) is a severe neurological complication of acute liver failure (ALF) characterized by the accumulation of neurotoxic metabolites and impaired cerebral function. We aimed to examine the correlation between HE severity and cerebrospinal fluid (CSF) biomarker levels in a rat model of ALF induced by subtotal hepatectomy.
Male Wistar rats underwent 92% hepatectomy and were monitored for neurological impairment via a standardized HE score. At twenty-four hours post surgery, CSF and blood were collected for biochemical analysis.
We found a significant positive correlation between neurological severity and CSF levels of glutamine (r = 0.929, < 0.001) and albumin (r = 0.869, < 0.001), both with HE grade I scores, highlighting their prominent role as HE biomarkers. Other amino acids, including aspartate (r = 0.790, < 0.001), glutamate (r = 0.853, < 0.001), isoleucine (r = 0.834, < 0.001), leucine (r = 0.813, < 0.001), lysine (r = 0.861, < 0.001), methionine (r = 0.889, < 0.001), phenylalanine (r = 0.916, < 0.001), ornithine (r = 0.775, < 0.001), tryptophan (r = 0.814, < 0.001), and valine (r = 0.721, < 0.001), also showed significant correlations with HE severity but not with HE grade I scores.
These findings underscore the potential of glutamine and albumin in CSF as key biomarkers for assessing neurological severity in ALF patients.
背景/目的：肝性脑病（HE）是急性肝衰竭（ALF）的一种严重神经并发症，其特征为神经毒性代谢产物的蓄积和脑功能受损。我们旨在研究在肝大部切除诱导的ALF大鼠模型中，HE严重程度与脑脊液（CSF）生物标志物水平之间的相关性。
雄性Wistar大鼠接受92%肝切除术，并通过标准化的HE评分监测神经功能损害。术后24小时，采集CSF和血液进行生化分析。
我们发现神经严重程度与CSF谷氨酰胺水平（r = 0.929，< 0.001）和白蛋白水平（r = 0.869，< 0.001）均呈显著正相关，二者均与HE I级评分相关，突出了它们作为HE生物标志物的重要作用。其他氨基酸，包括天冬氨酸（r = 0.790，< 0.001）、谷氨酸（r = 0.853，< 0.001）、异亮氨酸（r = 0.834，< 0.001）、亮氨酸（r = 0.813，< 0.001）、赖氨酸（r = 0.861，< 0.001）、蛋氨酸（r = 0.889，< 0.001）、苯丙氨酸（r = 0.916，< 0.001）、鸟氨酸（r = 0.775，< 0.001）、色氨酸（r = 0.814，< 0.001）和缬氨酸（r = 0.721，< 0.001），也与HE严重程度呈显著相关，但与HE I级评分无关。
这些发现强调了CSF中谷氨酰胺和白蛋白作为评估ALF患者神经严重程度关键生物标志物的潜力。
