AMMONIA - KEY FACTOR IN THE PATHOGENESIS OF HEPATIC-ENCEPHALOPATHY
AMMONIA - KEY FACTOR IN THE PATHOGENESIS OF HEPATIC-ENCEPHALOPATHY
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DOI：
10.1007/bf02833598
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发表时间：
1987-02-01
期刊：
影响因子：
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通讯作者：
LAYRARGUES, GP
中科院分区：
文献类型：
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作者：
BUTTERWORTH, RF;GIGUERE, JF;LAYRARGUES, GP
大量临床和实验证据表明，氨毒性是与亚急性和慢性肝病相关的肝性脑病发病机制的主要因素。严重肝病患者的血液和脑脊液 (CSF) 中的氨水平经常升高。肝性脑病导致的神经病理学损伤（阿尔茨海默病 II 型星形细胞增多症）与尿素循环酶遗传缺陷引起的先天性高氨血症患者的神经病理学损伤类似。大鼠门腔静脉吻合术后，血氨浓度增加2倍，脑氨浓度增加2-3倍。对进行门腔静脉吻合术的大鼠施用氨盐或氨树脂会导致昏迷和阿尔茨海默病 II 型星形细胞增多症。由于中枢神经系统缺乏有效的尿素循环活动，大脑清除氨依赖于谷氨酰胺的形成。发现患有脑病的肝硬化患者和门腔静脉吻合术后的大鼠的脑脊液和脑谷氨酰胺显着升高。在这两种情况下，谷氨酰胺均以区域依赖性方式升高。已经提出了几种机制来解释氨的神经毒性作用。这些机制包括： (i) 血脑屏障运输的改变； (ii) 大脑能量代谢的改变； (iii) 对神经元膜的直接作用； (iv) 可释放谷氨酸的合成减少，导致谷氨酸能神经传递受损。
There is substantial clinical and experimental evidence to suggest that ammonia toxicity is a major factor in the pathogenesis of hepatic encephalopathy associated with subacute and chronic liver disease. Ammonia levels in patients with severe liver disease are frequently found to be elevated both in blood and cerebrospinal fluid (csf). Hepatic encephalopathy results in neuropathological damage of a similar nature (Alzheimer type II astrocytosis) to that found in patients with congenital hyperammonemia resulting from inherited defects of urea cycle enzymes. Following portocaval anastomosis in the rat, blood ammonia concentration is increased 2-fold, and brain ammonia is found to be increased 2–3-fold. Administration of ammonia salts or resins to rats with a portocaval anastomosis results in coma and in Alzheimer type II astrocytosis. Since the CNS is devoid of effective urea cycle activity, ammonia removal by brain relies on glutamine formation. Cerebrospinal fluid and brain glutamine are found to be significantly elevated in cirrhotic patients with encephalopathy and in rats following portocaval anastomosis. In both cases, glutamine is found to be elevated in a region-dependent manner. Several mechanisms have been proposed to explain the neurotoxic action of ammonia. Such mechanisms include: (i) Modification of blood-brain barrier transport; (ii) alterations of cerebral energy metabolism; (iii) direct actions on the neuronal membrane; and (iv) decreased synthesis of releasable glutamate, resulting in impaired glutamatergic neurotransmission.