Girard G, Giguère J F, Butterworth R F
Neuroscience Research Unit, Hopital Saint-Luc (University of Montreal), Quebec, Canada.
Metab Brain Dis. 1993 Dec;8(4):207-15. doi: 10.1007/BF01001062.
Portacaval anastomosis in the rat results in liver atrophy, sustained hyperammonemia and mild encephalopathy. Previous studies have demonstrated region-selective alterations of glutamine and other ammonia-related amino acids in brain following portacaval anastomosis. Ammonia removal by brain relies on glutamine synthesis and the enzyme responsible, glutamine synthetase, has an almost exclusively astrocytic localization. Glutamine synthetase activities were measured using a radioenzymatic assay in homogenates of seven brain regions of rats four weeks after end-to-side portacaval anastomosis. Enzyme activities were significantly reduced in hippocampus (by 25%, p < 0.01), in cerebellum (by 29%, p < 0.01) and in cerebral cortex (by 14%, p < 0.05). Enzyme activities in other brain regions were within normal limits. Region-selective reductions of glutamine synthetase following portacaval anastomosis could result in disruption of neuron-glial metabolic interactions and in a deficit of glutamatergic synaptic regulation. Similar mechanisms could be implicated in the pathogenesis of hepatic encephalopathy accompanying chronic liver disease in humans.
大鼠门腔静脉吻合术会导致肝脏萎缩、持续性高氨血症和轻度脑病。先前的研究表明，门腔静脉吻合术后大脑中谷氨酰胺和其他与氨相关的氨基酸存在区域选择性改变。大脑清除氨依赖于谷氨酰胺的合成，而负责该合成的酶——谷氨酰胺合成酶几乎只定位于星形胶质细胞。在大鼠端侧门腔静脉吻合术后四周，使用放射酶法测定了七个脑区匀浆中的谷氨酰胺合成酶活性。海马体（降低25%，p < 0.01）、小脑（降低29%，p < 0.01）和大脑皮层（降低14%，p < 0.05）中的酶活性显著降低。其他脑区的酶活性在正常范围内。门腔静脉吻合术后谷氨酰胺合成酶的区域选择性降低可能导致神经元-胶质细胞代谢相互作用的破坏以及谷氨酸能突触调节的缺陷。类似的机制可能与人类慢性肝病伴发的肝性脑病的发病机制有关。
