Glutamate‐induced activation of nitric oxide synthase is impaired in cerebral cortex in vivo in rats with chronic liver failure
Glutamate‐induced activation of nitric oxide synthase is impaired in cerebral cortex in vivo in rats with chronic liver failure
复制标题
慢性肝衰竭大鼠体内大脑皮层谷氨酸诱导的一氧化氮合酶激活受损
DOI：
10.1111/j.1471-4159.2006.04446.x
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发表时间：
2007
影响因子：
4.7
通讯作者：
V. Felipo
中科院分区：
文献类型：
--
作者：
R. Rodrigo;S. Erceg;J. Rodríguez;J. Sáez;Blanca Piedrafita;I. Suárez;V. Felipo
已经提出脑中谷氨酸-一氧化氮-环磷酸鸟苷（cGMP）通路的损伤有助于肝性脑病的认知障碍。这项工作的目的是评估是否这一途径的功能和一氧化氮合酶（NOS）在体内的慢性肝衰竭，由于门腔静脉分流（PCS），以及是否这些改变是由于高血氨症大鼠大脑皮层的改变。通过PCS和对照大鼠以及无肝功能衰竭的高氨血症大鼠大脑皮质中的体内微透析分析谷氨酸-一氧化氮-cGMP通路功能和NMDA对NOS的激活。在这些大鼠的皮层切片和暴露于氨的培养皮层神经元中进行了类似的研究。高氨血症或肝功能衰竭大鼠大脑皮质基础NOS活性、亚硝酸盐和cGMP升高。这些增加似乎是由于诱导型一氧化氮合酶表达增加。在两种动物模型和暴露于氨的神经元中，NMDA对NOS的激活在大脑皮层中受损。慢性肝功能衰竭增加基础NOS活性、一氧化氮和cGMP，但减少由NMDA受体激活诱导的NOS激活。高氨血症是两种效应的原因，这两种效应将独立导致肝性脑病神经系统改变。
It has been proposed that impairment of the glutamate‐nitric oxide‐cyclic guanosine monophosphate (cGMP) pathway in brain contributes to cognitive impairment in hepatic encephalopathy. The aims of this work were to assess whether the function of this pathway and of nitric oxide synthase (NOS) are altered in cerebral cortex in vivo in rats with chronic liver failure due to portacaval shunt (PCS) and whether these alterations are due to hyperammonemia. The glutamate‐nitric oxide‐cGMP pathway function and NOS activation by NMDA was analysed by in vivo microdialysis in cerebral cortex of PCS and control rats and in rats with hyperammonemia without liver failure. Similar studies were done in cortical slices from these rats and in cultured cortical neurons exposed to ammonia. Basal NOS activity, nitrites and cGMP are increased in cortex of rats with hyperammonemia or liver failure. These increases seem due to increased inducible nitric oxide synthase expression. NOS activation by NMDA is impaired in cerebral cortex in both animal models and in neurons exposed to ammonia. Chronic liver failure increases basal NOS activity, nitric oxide and cGMP but reduces activation of NOS induced by NMDA receptors activation. Hyperammonemia is responsible for both effects which will lead, independently, to alterations contributing to neurological alterations in hepatic encephalopathy.
影响因子：
56.9
作者：
Sattler, R;Xiang, ZG;Tymianski, M
通讯作者：
Tymianski, M