Effects of long-term ethanol administration in a rat total enteral nutrition model of alcoholic liver disease
Effects of long-term ethanol administration in a rat total enteral nutrition model of alcoholic liver disease
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DOI：
10.1152/ajpgi.00145.2010
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发表时间：
2011-01-01
影响因子：
4.5
通讯作者：
Petersen, Dennis R.
中科院分区：
文献类型：
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作者：
Ronis, Martin J. J.;Hennings, Leah;Petersen, Dennis R.
雄性Sprague-Dawley大鼠通过全肠内营养（TEN）或乙醇（EtOH）等热量替代碳水化合物热量的相同饮食长期饲喂高不饱和脂肪饮食130天。另外的组在第1.7天补充抗氧化剂N-乙酰半胱氨酸（NAC）。g.kg相对于自由进食组，高脂饮食对照组的脂肪酸转运蛋白CD 36 mRNA的表达增加了3 - 4倍，并出现了轻度脂肪变性，但几乎没有其他肝脏病理学变化。与对照组相比，NAC治疗导致体细胞生长增加（4.0 +/-0.1 g/d vs. 3.1 +/- 0.1 g/d），肝脂肪变性评分增加（3.5 +/- 0.6 vs. 2.7 +/- 1.2），与甘油三酯水解蛋白脂尿苷的抑制有关，但血清丙氨酸氨基转移酶（ALT）未升高。慢性乙醇处理增加了脂肪酸转运蛋白FATP-2 mRNA的表达的两倍，导致显着的肝脂肪变性，氧化应激，血清ALT的两倍升高。然而，没有观察到肿瘤坏死因子-α或转化生长因子-β表达的变化。通过Masson三色和苦味酸天狼星红染色测量的纤维化，以及I型和III型胶原mRNA表达的两倍增加，仅在EtOH处理后观察到。长期乙醇处理增加肝细胞增殖，但没有修改hedgehog途径配体或靶基因或调节上皮细胞间质转化的基因的肝mRNA。虽然NAC对EtOH诱导的纤维化的影响不能完全评估，但NAC对肝细胞增殖具有累加作用，并防止EtOH诱导的氧化应激和坏死，尽管未能逆转肝脂肪变性。
Male Sprague-Dawley rats were chronically fed a high-unsaturated-fat diet for 130 days by using total enteral nutrition (TEN), or the same diet in which ethanol (EtOH) isocalorically replaced carbohydrate calories. Additional groups were supplemented with the antioxidant N-acetylcysteine (NAC) at 1.7 g.kg(-1).day(-1). Relative to an ad libitum chow-fed group, the high-fat-fed controls had three-to fourfold greater expression of fatty acid transporter CD36 mRNA and developed mild steatosis but little other hepatic pathology. NAC treatment resulted in increased somatic growth relative to controls (4.0 +/- 0.1 vs. 3.1 +/- 0.1 g/day) and increased hepatic steatosis score (3.5 +/- 0.6 vs. 2.7 +/- 1.2), associated with suppression of the triglyceride hydrolyzing protein adiponutrin, but produced no elevation in serum alanine aminotransferase (ALT). Chronic EtOH treatment increased expression of fatty acid transport protein FATP-2 mRNA twofold, resulting in marked hepatic steatosis, oxidative stress, and a twofold elevation in serum ALT. However, no changes in tumor necrosis factor-alpha or transforming growth factor-beta expression were observed. Fibrosis, as measured by Masson's trichrome and picrosirius red staining, and a twofold increase in expression of type I and type III collagen mRNA, was only observed after EtOH treatment. Long-term EtOH treatment increased hepatocyte proliferation but did not modify the hepatic mRNAs for hedgehog pathway ligands or target genes or genes regulating epithelial-to-mesenchymal transition. Although the effects of NAC on EtOH-induced fibrosis could not be fully evaluated, NAC had additive effects on hepatocyte proliferation and prevented EtOH-induced oxidative stress and necrosis, despite a failure to reverse hepatic steatosis.