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肝前性门静脉高压大鼠的高氨血症、脑水肿及血脑屏障改变与对乙酰氨基酚中毒

Hyperammonemia, brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paracetamol intoxication.

作者信息

Scorticati Camila, Prestifilippo Juan P, Eizayaga Francisco X, Castro José L, Romay Salvador, Fernández María A, Lemberg Abraham, Perazzo Juan C

机构信息

Cátedra de Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.

出版信息

World J Gastroenterol. 2004 May 1;10(9):1321-4. doi: 10.3748/wjg.v10.i9.1321.

Abstract

AIM

To study the blood-brain barrier integrity, brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication.

METHODS

Adults male Wistar rats were divided into four groups. Group I: sham operation; II: Prehepatic portal hypertension, produced by partial portal vein ligation; III: Acetaminophen intoxication and IV: Prehepatic portal hypertension plus acetaminophen. Acetaminophen was administered to produce acute hepatic injury. Portal pressure, liver serum enzymes and ammonia plasma levels were determined. Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity. Reflexes and behavioral tests were recorded.

RESULTS

Portal hypertension was significantly elevated in groups II and IV. Liver enzymes and ammonia plasma levels were increased in groups II, III and IV. Prehepatic portal hypertension (group II), acetaminophen intoxication (group III) and both (group IV) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia. Cortical edema was present in rats with acute hepatic injury in groups III and IV. Behavioral test (rota rod) was altered in group IV.

CONCLUSION

These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (cytotoxic). Group IV, with behavioral altered test, can be considered as a model for study at an early stage of portal-systemic encephalopathy.

摘要

目的

研究有无急性肝中毒的肝前性门静脉高压大鼠的血脑屏障完整性、脑水肿、动物行为及血浆氨水平。

方法

成年雄性Wistar大鼠分为四组。第一组:假手术;第二组:通过部分门静脉结扎产生肝前性门静脉高压;第三组:对乙酰氨基酚中毒;第四组:肝前性门静脉高压加对乙酰氨基酚。给予对乙酰氨基酚以产生急性肝损伤。测定门静脉压力、肝血清酶及血浆氨水平。记录脑皮质含水量,并使用台盼蓝研究血脑屏障完整性。记录反射和行为测试。

结果

第二组和第四组门静脉高压显著升高。第二组、第三组和第四组肝酶及血浆氨水平升高。肝前性门静脉高压(第二组)、对乙酰氨基酚中毒(第三组)及两者同时存在(第四组)均有血脑屏障完整性(台盼蓝)改变及高氨血症。第三组和第四组急性肝损伤大鼠出现皮质水肿。第四组行为测试(转棒试验)改变。

结论

这些结果提示存在另一种导致皮质水肿的途径,因为血脑屏障改变(血管源性)且出现高氨血症(细胞毒性)。行为测试改变的第四组可被视为门静脉-体循环性脑病早期研究的模型。

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