Simvastatin for rats with thioacetamide-induced liver failure and encephalopathy
Simvastatin for rats with thioacetamide-induced liver failure and encephalopathy
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DOI：
10.1111/j.1440-1746.2007.04988.x
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发表时间：
2008-07-01
影响因子：
4.1
通讯作者：
Lee, Shou-Dong
中科院分区：
文献类型：
--
作者：
Huang, Hui-Chun;Wang, Sun-Sang;Lee, Shou-Dong
背景与目的：一氧化氮(NO)抑制可加重硫代乙酰胺(TAA)所致急性肝功能衰竭大鼠的肝损伤和脑病，增加死亡率。他汀类药物除了降低血脂能力外，还能促进一氧化氮合酶的表达，但对脑病的影响尚不清楚。本研究旨在观察辛伐他汀对TAA所致大鼠急性肝损伤和肝性脑病的影响。方法：SD大鼠给予TAA(350 mg/kg/d)或生理盐水(NS)，连续3d。注射前2d，每组分成3组，分别给予蒸馏水、辛伐他汀(20 mg/kg/d)或辛伐他汀加N-硝基-L-精氨酸甲酯(L，25 mg/kg/d)灌胃，连续5d。结果：与NS组比较，TAA组大鼠血清ALT、AST、总胆红素、血氨水平明显升高，运动功能明显下降。在TAA治疗亚组中，辛伐他汀治疗组大鼠的运动活动计数和存活率高于生理盐水组(P=0.043)，而ALT、AST、胆红素和氨水平则有降低的趋势。所有接受辛伐他汀加L治疗的大鼠在注射三七总皂苷的过程中或之后均死亡。结论：辛伐他汀改善了三七总皂苷注射大鼠的脑病和存活。这种有益的作用被L的名字所抵消，这表明NO在肝损伤和脑病中的作用。
Background and Aim: Nitric oxide (NO) inhibition aggravates hepatic damage and encephalopathy and increases mortality in rats with thioacetamide (TAA)-induced acute liver failure. Statins enhance NO synthase expression beyond their lipid-lowering capability, but the impact on encephalopathy remains unexplored. The aim of this study was to assess the effects of simvastatin on rats with TAA-induced acute liver damage and hepatic encephalopathy.Methods: Sprague-Dawley rats received TAA (350 mg/kg/day) or normal saline (NS) by intraperitoneal injection for 3 consecutive days. Two days before injections, each group was divided into three subgroups, taking (i) distilled water; (ii) simvastatin (20 mg/kg/day); or (iii) simvastatin plus N-G-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg/day) by oral gavage for 5 days. On the fifth day, severity of encephalopathy was assessed and plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and ammonia were measured.Results: The TAA subgroups showed higher ALT, AST, bilirubin and ammonia levels and lower motor activity counts as compared with the NS subgroups. Among the TAA-treated subgroups, rats with simvastatin treatment exerted higher motor activity counts and survival rate (P = 0.043), and a trend of lower ALT, AST, bilirubin and ammonia levels than those receiving saline. All rats that underwent simvastatin plus L-NAME treatment died during or after TAA injections.Conclusions: Simvastatin improved encephalopathy and survival in TAA-administered rats. The beneficial effect was offset by L-NAME, suggesting the role of NO in liver damage and encephalopathy.