Pentoxifylline attenuates steatohepatitis induced by the methionine choline deficient diet
Pentoxifylline attenuates steatohepatitis induced by the methionine choline deficient diet
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DOI：
10.1016/j.jhep.2004.06.030
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发表时间：
2004-10-01
影响因子：
25.7
通讯作者：
Green, RM
中科院分区：
文献类型：
--
作者：
Koppe, SWP;Sahai, A;Green, RM
背景/目的：以蛋氨酸胆碱缺乏(MCD)饮食喂养小鼠是一种非酒精性脂肪性肝炎(NASH)的营养模型。NASH和酒精诱导的脂肪性肝炎在组织学上相似，提示有类似的发病机制。己酮可可碱(PTX)可减少酒精性脂肪性肝炎患者肿瘤坏死因子-α的产生，作为一种抗氧化剂并降低死亡率。本研究的目的是确定PTX是否能减轻MCD饮食诱导的脂肪性肝炎，并确定其作用机制。方法：将小鼠分为两组，分别给予MCD和对照组饲料，分别给予或不给予PTX治疗。结果：PTX可减轻MCD饮食诱导的脂肪性肝炎，降低血清ALT水平，降低肝脏炎症反应。与MCD组相比，MCD+PTX组的血清ALT水平降低了约50%。MCD+PTX组的肝脏谷胱甘肽水平显著高于MCD组。服用PTX的雌性小鼠的肿瘤坏死因子-α基因表达也降低。与MCD组小鼠相比，MCD+PTX组小鼠肝脏甘油三酯含量增加，但尽管脂肪变性增加，但炎症的组织学证据较少。结论：PTX可降低脂肪性肝炎MCD模型小鼠血清ALT水平，降低肝脏炎症反应，其机制可能与提高谷胱甘肽水平或降低肿瘤坏死因子-α的表达有关。(C)2004年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background/Aims: Feeding mice a methionine choline deficient (MCD) diet serves as a nutritional model of nonalcoholic steatohepatitis (NASH). NASH and alcohol-induced steatohepatitis are histologically similar, suggesting a similar pathogenesis. Pentoxifylline (PTX) attenuates TNF-alpha production, acts as an antioxidant and decreases mortality in alcoholic steatohepatitis. The aim of our study is to determine if PTX attenuates MCD diet induced steatohepatitis and determine the mechanism of this effect.Methods: Mice were placed on an MCD or control diet for 2 weeks and were treated with or without PTX. Serum ALT, liver histology, and inflammatory mechanisms were evaluated.Results: PTX attenuates MCD diet induced steatohepatitis, decreasing both serum ALT levels and hepatic inflammation. Serum ALT levels were reduced approximately 50% in the MCD+PTX group compared to the MCD group. Hepatic glutathione levels were significantly higher in the MCD+PTX group compared to the MCD group. There was also a reduction in TNF-alpha mRNA in female mice treated with PTX. MCD+PTX mice had increased hepatic triglyceride content compared to the MCD mice, but less histologic evidence of inflammation despite the increased steatosis. Serum lipid and bile salt levels also were similar in PTX and vehicle control treated mice.Conclusions: PTX decreases serum ALT levels and hepatic inflammation in the MCD model of steatohepatitis, likely via increasing glutathione levels or reducing TNF-alpha expression. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.