肝性脑病发病机制的研究进展

肝性脑病(hepatic encephalopathy,HE)是肝功能严重障碍和/或门体分流术后患者发生的以代谢紊乱为基础,神经、精神症状为主要表现的综合征.其症状包括意识混乱、定向力障碍、协调能力降低,甚至昏迷.其发病机制被认为是高氨血症使脑星形胶质细胞内谷氨酰胺浓度升高、钙离子内流启动氧化应激、破坏线粒体功能,干扰能量代谢并诱发炎症反应,破坏血脑屏障使内皮细胞、脑星形胶质细胞对水通透性增加,引发脑水肿.炎症反应又反过来升高脑内氨浓度,增加其中枢神经系统毒性,而锰是参与上述过程的重要组成成分,故目前公认为高氨血症和炎症反应的协同作用导致星形胶质细胞肿胀,进而引起脑水肿导致HE.本文就HE发病机制的研究进展作一综述.

Progress in understanding the pathogenesis of hepatic encephalopathy

Hepatic encephalopathy(HE) is a serious neuropsychiatric complication of both acute and chronic liver diseases.Symptoms of HE can include confusion,disorientation,poor coordination,and even coma.The pathogenesis of HE was thought to involve the increase in blood levels of ammonia,which increases the intracellular levels of glutamine,promotes calcium influx and initiates oxidative stress,destroys the function of mitochondria,disrupts energy metabolism and causes inflammation,destroys blood brain barrier,increases the water permeability of brain endothelial cells and astrocytes,and then induces brain edema.While,inflammation,in turn,raises the ammonia levels in the brain,which is toxic to the central nervous system.Manganese is an important component which participates in the above processes.A general consensus exists that the synergistic effects of excess ammonia and inflammation cause astrocyte swelling and cerebral edema;however,the precise molecular mechanisms that lead to these morphological changes in the brain are unclear.This article will summarize the research progress in understanding the pathogenesis of HE.