Rössle M, Deckert J, Mullen K D, Jones D B, Grün M, Gerok W, Jones E A
Digestive Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Z Gastroenterol. 1990 Mar;28(3):142-6.
Quantitative autoradiography was used to assess the densities of gamma-aminobutyric acid (GABAA) receptors in the brains of rats with a portacaval end-to-side shunt (PCA). The shunt alone induced only mild encephalopathy with ataxia and decreased locomotion. Aggravation of the encephalopathy was achieved by gavage feeding of packed erythrocytes or by induction of severe hyperammonemia by intraperitoneal injection of urease. Gavage feeding of erythrocytes led to severe encephalopathy in about 50% of the animals with PCA. The combination of PCA and urease treatment caused severe encephalopathy in every animal. The serum ammonia concentration increased 5 times normal by PCA alone, 20 times normal by gavage feeding of erythrocytes and more than 30 times normal by urease-treatment of the PCA-animals. For autoradiography, coronal slices were cut at the level of the hippocampal formation and through the cerebellum. Radioligand binding was measured using as a ligand 3H-muscimol, a specific GABAA receptor agonist. The specific binding of 3H-muscimol was assessed densitometrically in several microregions of cerebral cortex, hippocampus and cerebellar cortex. No significant differences were observed between the magnitude of ligand binding to specific microregions of brains from normal animals, animals with PCA without overt encephalopathy and animals with severe encephalopathy induced by a combination of PCA and gavage feeding of erythrocytes or urease treatment.
采用定量放射自显影术评估门腔静脉端侧分流术(PCA)大鼠脑内γ-氨基丁酸(GABAA)受体的密度。单纯分流仅诱发轻度脑病,伴有共济失调和运动减少。通过灌胃给予浓缩红细胞或腹腔注射脲酶诱导严重高氨血症可使脑病加重。对约50%接受PCA的动物灌胃给予红细胞会导致严重脑病。PCA与脲酶治疗联合应用使每只动物均出现严重脑病。单纯PCA使血清氨浓度升至正常的5倍,灌胃给予红细胞使其升至正常的20倍,对接受PCA的动物进行脲酶治疗使其升至正常的30倍以上。进行放射自显影时,在海马结构水平及通过小脑切取冠状切片。使用3H-蝇蕈醇(一种特异性GABAA受体激动剂)作为配体测量放射性配体结合。在大脑皮质、海马和小脑皮质的几个微区通过密度测定评估3H-蝇蕈醇的特异性结合。在正常动物、无明显脑病的PCA动物以及PCA与灌胃给予红细胞或脲酶治疗联合诱导严重脑病的动物的脑特定微区,未观察到配体结合量有显著差异。