Butterworth R F, Le O, Lavoie J, Szerb J C
Laboratory of Neurochemistry, André-Viallet Clinical Research Centre, Hôpital St.-Luc (University of Montreal), Quebec, Canada.
J Neurochem. 1991 May;56(5):1481-4. doi: 10.1111/j.1471-4159.1991.tb02041.x.
To evaluate the effects of chronic liver failure on release of the excitatory transmitter glutamate, electrically stimulated Ca2(+)-dependent and Ca2(+)-independent release of glutamate in the absence or presence of NH4+ was studied in superfused slices of hippocampus from portacaval-shunted or sham-operated rats 4 weeks after surgery. Spontaneous and stimulation-evoked release of glutamate was higher in shunted rats in the presence of normal or low Ca2+ concentrations, and this release was depressed by 5 mM ammonium chloride. These findings suggest that portacaval shunting results in increased levels of extracellular glutamate in brain, probably due to a decreased reuptake of glutamate into perineuronal astrocytes, shown in previous studies to undergo neuropathological changes following portacaval shunting. Changes in the inactivation of transmitter glutamate could be responsible, at least in part, for the neurological dysfunction resulting from sustained hyperammonemia and portal-systemic shunting resulting from chronic liver failure.
为评估慢性肝功能衰竭对兴奋性递质谷氨酸释放的影响，我们对术后4周的门腔分流或假手术大鼠海马脑片进行了研究，观察在有无NH4+存在的情况下，电刺激诱发的依赖Ca2+和不依赖Ca2+的谷氨酸释放情况。在正常或低Ca2+浓度存在时，分流大鼠中谷氨酸的自发释放和刺激诱发释放均较高，且这种释放可被5 mM氯化铵抑制。这些发现表明，门腔分流导致脑内细胞外谷氨酸水平升高，这可能是由于向神经周星形胶质细胞内的谷氨酸再摄取减少所致，先前的研究表明，门腔分流后星形胶质细胞会发生神经病理变化。递质谷氨酸失活的改变可能至少部分地导致了慢性肝功能衰竭所致持续高氨血症和门体分流引起的神经功能障碍。
