HEPATIC-ENCEPHALOPATHY IN CIRRHOTIC AND PORTACAVAL SHUNTED DOGS - LACK OF CHANGES IN BRAIN GABA UPTAKE, BRAIN GABA LEVELS, BRAIN GLUTAMIC-ACID DECARBOXYLASE ACTIVITY AND BRAIN POSTSYNAPTIC GABA RECEPTORS
HEPATIC-ENCEPHALOPATHY IN CIRRHOTIC AND PORTACAVAL SHUNTED DOGS - LACK OF CHANGES IN BRAIN GABA UPTAKE, BRAIN GABA LEVELS, BRAIN GLUTAMIC-ACID DECARBOXYLASE ACTIVITY AND BRAIN POSTSYNAPTIC GABA RECEPTORS
复制标题
DOI：
10.1002/hep.1840080424
复制
发表时间：
1988-07-01
期刊：
影响因子：
13.5
通讯作者：
HUET, PM
中科院分区：
文献类型：
--
作者：
ROY, S;POMIERLAYRARGUES, G;HUET, PM
从暴发性肝衰竭的兔模型的研究中已经提出，肝性脑病可能与脑γ-过氧化氢的增加有关。通过更具渗透性的血脑屏障摄取氨基丁酸，导致脑γ-氨基丁酸的过度活动。氨基丁酸介导的抑制性神经传递。五组狗进行了研究：正常狗，狗与继发性胆汁性肝硬化与肝性脑病和门腔静脉分流犬与肝性脑病。脑γ-在未麻醉的狗中使用多指示剂稀释曲线技术研究氨基丁酸和蔗糖摄取。99 mTc标记的白蛋白（细胞外参照物质）的示踪剂剂量，3 H标记的γ-将在自体狗血浆中制备的氨基丁酸和14 C标记的蔗糖注射到一侧颈动脉中，并获得背侧矢状窦稀释曲线。通过比较99 mTc-标记的白蛋白和[3 H] γ下的面积计算摄取。氨基丁酸（或[14 C]蔗糖）从外观到峰高的曲线。杀人后，大脑. γ. -通过高效液相色谱法测量额叶皮层中的氨基丁酸水平，并使用放射酶测定法测量谷氨酸脱羧酶活性。脑γ-使用[3 H]蝇蕈醇结合研究评估氨基丁酸突触后受体。在患有或不患有肝性脑病的中风和分流的狗中，脑γ-淀粉酶没有显著变化。氨基丁酸和蔗糖摄取，脑γ-氨基丁酸水平和谷氨酸脱羧酶活性。[3 H]蝇蕈醇结合研究未显示突触后γ-受体的数量和亲和力的任何变化。氨基丁酸受体此外，在4只肝性脑病犬中注射台盼蓝并没有引起脑染色。这些发现既不支持脑γ的选择性增加，肝性脑病中的氨基丁酸摄取也不是血脑屏障的物理破坏。此外，脑研究表明，受损的中枢γ-氨基丁酸能功能在肝硬化或门腔静脉分流犬的肝性脑病发病机制中不起重要作用。
It has been suggested, from studies of a rabbit model of fulminant hepatic failure, that hepatic encephalopathy might be related to an increase in brain .gamma.-aminobutyric acid uptake through a more permeable blood-brain barrier, leading to an overactivity of brain .gamma.-aminobutyric acid-mediated inhibitory neurotransmission. Five groups of dogs were studied: normal dogs, dogs with secondary biliary cirrhosis without and with hepatic encephalopathy and portacaval shunted dogs without and with hepatic encephalopathy. Brain .gamma.-aminobutyric acid and sucrose uptake was investigated using the multiple indicator dilution curve technique in unanesthetized dogs. Tracer doses of 99mTc-labeled albumin (extracellular reference substance), 3H-labeled .gamma.-aminobutyric acid and 14C-labeled sucrose prepared in autologous dog plasma were injected in one carotid artery, and dorsal sagittal sinus dilution curves were obtained. Uptake was calculated by comparing the areas under the 99mTc-labeled albumin and the [3H].gamma.-aminobutyric acid (or [14C]sucrose) curves from appearance to peak height. After killing, brain .gamma.-aminobutyric acid levels were measured in the frontal cortex by high-performance liquid chromatography and glutamic acid decarboxylase activities using a radioenzymatic assay. Brain .gamma.-aminobutyric acid postsynaptic receptors were assessed using [3H]muscimol binding studies. There were no significant changes in cirrhotic and shunted dogs with or without hepatic encephalopathy with regard to brain .gamma.-aminobutyric acid and sucrose uptake, brain .gamma.-aminobutyric acid levels and glutamic acid decarboxylase activities. [3H]Muscimol binding studies did not show any changes in the number nor in the affinity of postsynaptic .gamma.-aminobutyric acid receptors. Moreover, trypan blue injected in four dogs with hepatic encephalopathy did not induce a staining of the brain. These findings support neither a selective increase in brain .gamma.-aminobutyric acid uptake in hepatic encephalopathy nor a physical breakdown of the blood-brain barrier. Moreover, brain studies suggest that impaired central .gamma.-aminobutyric acid-ergic function does not play an important role in the pathogenesis of hepatic encephalopathy in dogs with cirrhosis or portacaval shunts.