Knecht K, Michalak A, Rose C, Rothstein J D, Butterworth R F
Neuroscience Research Unit, Hôpital Saint-Luc (University of Montreal), Quebec, Canada.
Neurosci Lett. 1997 Jul 4;229(3):201-3. doi: 10.1016/s0304-3940(97)00444-8.
It has been suggested that reduced astrocytic uptake of neuronally released glutamate contributes to the pathogenesis of hepatic encephalopathy in acute liver failure. In order to further address this issue, the recently cloned and sequenced astrocytic glutamate transporter GLT-1 was studied in brain preparations from rats with ischemic liver failure induced by portacaval anastomosis followed 24 h later by hepatic artery ligation and from appropriate sham-operated controls. GLT-1 expression was studied using reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of GLT-1 transcript was significantly decreased in frontal cortex at coma stages of acute liver failure. Western blotting using a polyclonal antibody to GLT-1 revealed a concomitant decrease in expression of transporter protein in the brains of rats with acute liver failure. Reduced capacity of astrocytes to reuptake neuronally released glutamate, resulting from a GLT-1 transporter deficit and the consequently compromised neuron-astrocytic trafficking of glutamate could contribute to the pathogenesis of hepatic encephalopathy and brain edema, two major complications of acute liver failure.
有人提出，星形胶质细胞对神经元释放的谷氨酸摄取减少有助于急性肝衰竭时肝性脑病的发病机制。为了进一步探讨这个问题，我们对最近克隆并测序的星形胶质细胞谷氨酸转运体GLT-1进行了研究，研究对象是门腔静脉吻合术诱导缺血性肝衰竭并在24小时后进行肝动脉结扎的大鼠脑标本，以及相应的假手术对照组。使用逆转录聚合酶链反应（RT-PCR）研究GLT-1的表达。在急性肝衰竭昏迷期，额叶皮质中GLT-1转录本的表达显著降低。使用针对GLT-1的多克隆抗体进行的蛋白质印迹显示，急性肝衰竭大鼠脑中转运蛋白的表达也随之降低。由于GLT-1转运体缺陷导致星形胶质细胞重新摄取神经元释放的谷氨酸的能力降低，进而损害了谷氨酸在神经元-星形胶质细胞之间的转运，这可能导致肝性脑病和脑水肿的发病机制，而这两种疾病是急性肝衰竭的两个主要并发症。
