神经甾体在肝性脑病中的研究进展

Role of neurosteroids in hepatic encephalopathy

肝性脑病(hepatic encephalopathy,HE)是由慢性或急性肝脏疾病引起的神经精神症候群的一种医学现象.神经甾体是以胆固醇及其前体为原料,由中枢神经系统多种细胞(神经元、少突胶质细胞、星形胶质细胞)合成.神经甾体通过基因和非基因效应参与HE的病理生理.一方面,神经甾体结合并调节不同的神经元膜受体,包括γ-氨基丁酸A受体(gamma amino butyric acid-A receptor,GABA-A)、N-甲基-D-天冬氨酸受体(N-methyl-Daspartic acid receptor,NMDA)、5-羟色胺3(5-hydroxytryptamine 3,5-HT3)受体及阿片受体等;另一方面,神经甾体结合于细胞内受体来调节基因表达.值得一提的是,神经甾体通过抑制海马突触活性的长时程增强效应(long-term potentiation,LTP)参与HE的病理生理.神经甾体有望为肝性脑病治疗提供新的途径.

Hepatic encephalopathy（HE） is a neuropsychiatric manifestation of chronic or acute liver disease. Neurosteroids are synthesized from cholesterol and its precursors by glial cells oligodendrocytes and neurons in the brain The mechanisms by which neurosteroids affect brain function may involve both genetic and non-genetic effects. On one hand, neurosteroids bind and modulate different types of neurona membrane receptors, including gamma-amino butyric acid-A receptor（GABA-A）, N-methylD-aspartic acid receptor（NMDA）, 5-hydroxytryptamine 3（5-HT3） and opioid receptors which have been showed to be involved inHE. On the other hand, some neurosteroids bind to intracellular receptors through which they also regulate gene expression. Of note, neurosteroids play a role in the pathogenesis of HE through inhibiting long-term potentiation. Neurosteroids might provide a new avenue for HE treatment.