Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Street, 02-106 Warsaw, Poland.
Int J Mol Sci. 2020 Oct 20;21(20):7750. doi: 10.3390/ijms21207750.
Acute liver failure (ALF) leads to neurological symptoms defined as hepatic encephalopathy (HE). Although accumulation of ammonia and neuroinflammation are generally accepted as main contributors to HE pathomechanism, a buildup of bile acids (BA) in the blood is a frequent component of liver injury in HE patients. Recent studies have identified the nuclear farnesoid X receptor (FXR) acting via small heterodimer partner (SHP) as a mediator of BA-induced effects in the brain of ALF animals. The present study investigated the status of the BA-FXR axis in the brain and the liver, including selective changes in pertinent genes in thioacetamide (TAA)-induced ALF in Sprague-Dawley rats. FXR was found in rat neurons, confirming earlier reports for mouse and human brain. BA accumulated in blood but not in the brain tissue. Expression of mRNAs coding for and was reduced in the hippocampus and of mRNA also in the cerebellum. Changes in mRNA levels were not followed by changes in FXR protein. The results leave open the possibility that mobilization of the BA-FXR axis in the brain may not be necessarily pathognomonic to HE but may depend upon ALF-related confounding factors.
急性肝衰竭（ALF）导致定义为肝性脑病（HE）的神经症状。尽管氨和神经炎症的积累通常被认为是 HE 发病机制的主要因素，但胆汁酸（BA）在血液中的积聚是 HE 患者肝损伤的常见成分。最近的研究已经确定核法尼醇 X 受体（FXR）通过小异二聚体伴侣（SHP）作为 ALF 动物大脑中 BA 诱导作用的介质。本研究调查了 BA-FXR 轴在大脑和肝脏中的状态，包括硫代乙酰胺（TAA）诱导的 Sprague-Dawley 大鼠 ALF 中相关基因的选择性变化。FXR 存在于大鼠神经元中，证实了先前对小鼠和人脑的报道。BA 在血液中积聚，但不在脑组织中积聚。编码 和 的 mRNA 在海马体中减少， 和 的 mRNA 也在小脑体中减少。 的 mRNA 水平的变化没有伴随 FXR 蛋白的变化。研究结果表明，BA-FXR 轴在大脑中的动员不一定是 HE 的特征，而可能取决于与 ALF 相关的混杂因素。
