Rodrigo R, Jover R, Candela A, Compañ A, Sáez-Valero J, Erceg S, Felipo V
Laboratory of Neurobiology, Fundación Valenciana de Investigaciones Biomédicas, Amadeo de Saboya 4, 46010 Valencia, Spain.
Neuroscience. 2005;130(2):435-43. doi: 10.1016/j.neuroscience.2004.09.027.
Modulation of soluble guanylate cyclase (sGC) by nitric oxide (NO) is altered in brain from cirrhotic patients. The aim of this work was to assess whether an animal model of cirrhosis, bile duct ligation, alone or combined with diet-induced hyperammonemia for 7-10 days reproduces the alterations in NO modulation of sGC found in brains from cirrhotic patients. sGC activity was measured under basal conditions and in the presence of NO in cerebellum and cerebral cortex of the following groups of rats: controls, bile duct ligation without or with hyperammonemia and hyperammonemia without bile duct ligation. In cerebellum activation of sGC by NO was significantly lower in bile duct ligated rats with (12 +/- five-fold) or without (14 +/- six-fold) hyperammonemia than in control rats (23 +/- seven-fold). In cerebral cortex activation of sGC by NO was higher in rats with bile duct ligation with hyperammonemia (124 +/- 30-fold) but not without hyperammonemia (59 +/- 15-fold) than in control rats (66 +/- 11-fold). The combination of bile duct ligation and hyperammonemia reproduces the alterations in the modulation of soluble guanylate cyclase by NO found in cerebral cortex and cerebellum of cirrhotic patients while bile duct ligation or hyperammonemia alone reproduces the effects in cerebellum but not in cerebral cortex.
肝硬化患者大脑中一氧化氮（NO）对可溶性鸟苷酸环化酶（sGC）的调节发生了改变。本研究的目的是评估肝硬化动物模型——胆管结扎术，单独或联合饮食诱导的高氨血症7 - 10天，是否会重现肝硬化患者大脑中发现的NO对sGC调节的改变。在以下几组大鼠的小脑和大脑皮层中，在基础条件下以及存在NO的情况下测量sGC活性：对照组、无高氨血症或有高氨血症的胆管结扎组以及无胆管结扎的高氨血症组。在小脑中，有（12±5倍）或无（14±6倍）高氨血症的胆管结扎大鼠中，NO对sGC的激活显著低于对照大鼠（23±7倍）。在大脑皮层中，有高氨血症的胆管结扎大鼠中NO对sGC的激活高于对照大鼠（66±11倍），分别为（124±30倍）和（59±15倍）。胆管结扎和高氨血症的联合重现了肝硬化患者大脑皮层和小脑中NO对可溶性鸟苷酸环化酶调节的改变，而单独的胆管结扎或高氨血症重现了小脑中的效应，但在大脑皮层中未重现。
