N-acetylcysteine attenuates progression of liver pathology in a rat model of nonalcoholic steatohepatitis.
N-acetylcysteine attenuates progression of liver pathology in a rat model of nonalcoholic steatohepatitis.
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DOI：
10.1093/jn/138.10.1872
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Ronis MJ
中科院分区：
文献类型：
--
作者：
Baumgardner JN;Shankar K;Hennings L;Albano E;Badger TM;Ronis MJ
已经提出了非酒精性脂肪性肝炎（NASH）的“两次打击”模型，其中脂肪变性构成“第一次打击”并使肝脏对导致NASH的潜在“第二次打击”敏感。氧化应激被认为是“第二次打击”的候选者。N-乙酰半胱氨酸（NAC）是一种抗氧化剂，已被建议作为NASH的饮食疗法。我们研究了NAC在大鼠全肠内营养（TEN）模型中的作用，在该模型中，NASH的发展是由于过度喂食膳食多不饱和脂肪的结果。雄性Sprague-Dawley大鼠随意喂食AIN-93 G颗粒饲料，或灌胃过量喂食含70%玉米油的9200 kJ steckg-0.75 stecd-1液体饲料（含或不含2 g steckg-1 stecd-1 NAC），持续65天。肝脏脂肪变性不受饮食补充NAC的影响;然而，肝脏病理学评分显著降低（p≤0.05），NAC对丙氨酸氨基转移酶释放提供部分保护（p≤0.05）。NAC减轻了肝脏氧化应激（TBARS; p≤0.05）的增加;防止了细胞色素P450 2 E1载脂蛋白和mRNA以及肿瘤坏死因子-α（TNF-α）mRNA的增加。相对于70%玉米油组，NAC组中观察到抗脂质过氧化产物加合蛋白的自身抗体滴度降低（p≤0.05）。NAC还减少了Picosirius红染色的胶原蛋白，纤维化的标志物。然而，肝星状细胞活化标志物不受影响。在TEN NASH模型中使用NAC，我们已经证明NAC通过减少氧化应激的发展和随后的TNF-α增加来预防NASH进展的许多方面，但不能阻断脂肪变性的发展。
A "two-hit" model for non-alcoholic steatohepatitis (NASH) has been proposed in which steatosis constitutes the "first hit" and sensitizes the liver to potential "second hits" resulting in NASH. Oxidative stress is considered a candidate for the "second hit". N-acetylcysteine (NAC), an antioxidant, has been suggested as a dietary therapy for NASH. We examined effects of NAC in a rat total enteral nutrition (TEN) model where NASH develops as the result of overfeeding dietary polyunsaturated fat. Male Sprague-Dawley rats were fed pelleted AIN-93G diets ad libitum or were overfed a 9200 kJ˙ kg−0.75˙d−1 liquid diet containing 70% corn oil with or without 2 g˙ kg−1˙d−1 NAC intragastrically for 65 d. Hepatic steatosis was not influenced by dietary supplementation with NAC; however, the liver pathology score was significantly lower (p≤0.05) and NAC provided partial protection against alanine aminotransferase release (p≤0.05). NAC attenuated increased hepatic oxidative stress (TBARS; p≤0.05); prevented increases in cytochrome P450 2E1 apoprotein and mRNA; and tumor necrosis factor-α (TNF-α) mRNA. A decrease in titers of auto-antibodies against proteins adducted to lipid peroxidation products was observed in the NAC group relative to the 70% corn oil group (p≤0.05). NAC also decreased Picosirius red staining of collagen, a marker of fibrosis. However, markers of hepatic stellate cell activation were unaffected. Using NAC in a TEN model of NASH we have demonstrated that NAC prevents many aspects of NASH progression by decreasing development of oxidative stress and subsequent increases in TNF-α, but is unable to block development of steatosis.
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DOI：
10.1164/ajrccm.162.1.9903129
发表时间：
2000-07-01
影响因子：
24.7
作者：
Hagiwara, S;Ishii, Y;Kitamura, S
通讯作者：
Kitamura, S
影响因子：
25.7
作者：
Koppe, SWP;Sahai, A;Green, RM
通讯作者：
Green, RM
影响因子：
2.3
作者：
BADGER, TM;RONIS, MJJ;HAKKAK, R
通讯作者：
HAKKAK, R
影响因子：
13.5
作者：
Hui, JM;Hodge, A;George, J
通讯作者：
George, J
影响因子：
13.5
作者：
Crespo, J;Cayón, A;Pons-Romero, F
通讯作者：
Pons-Romero, F