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中链甘油三酯对非酒精性脂肪性肝炎大鼠的有益作用与毒性

Beneficial effects versus toxicity of medium-chain triacylglycerols in rats with NASH.

作者信息

Lieber Charles S, DeCarli Leonore M, Leo Maria A, Mak Ki M, Ponomarenko Anatoly, Ren Chaoling, Wang Xiaolei

机构信息

Alcohol Research Center, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468, USA.

出版信息

J Hepatol. 2008 Feb;48(2):318-26. doi: 10.1016/j.jhep.2007.09.016. Epub 2007 Dec 10.

Abstract

BACKGROUND/AIMS: Replacing long-chain triacylglycerols (LCT) with medium-chain triacylglycerols (MCT) reduces alcohol-induced liver injury. Because of the similarity of the pathogenesis of alcohol-induced liver damage and non-alcoholic steatohepatitis (NASH), our aim was to assess whether MCT is also beneficial in NASH.

METHODS

We used a rat NASH model in which corn oil (35% of total calories) was isocalorically replaced with MCT.

RESULTS

Partial replacement of LCT did not ameliorate hepatic fat accumulation, 4-hydroxynonenal, collagen type I and its mRNA but it increased TNF-alpha and its mRNA (p<0.001). However, in rats given the high-fat diet restricted to 2/3 of the amount they were consuming, these adverse effects decreased, with and without MCT including less liver steatosis and lower triacylglycerols, but without beneficial effects of MCT. When 70% of the fat calories were replaced with MCT with no LCT remaining in the diet, no steatosis developed and hepatic TNF-alpha was low. When all MCT were given with carbohydrates (instead of LCT) hepatic TNF-alpha also decreased (p<0.001).

CONCLUSIONS

MCT are not hepatotoxic, provided the diet contains no significant amount of LCT. Total replacement of dietary LCT with MCT fed ad libitum is beneficial whereas partial replacement becomes hepatotoxic, unless the dietary intake is restricted.

摘要

背景/目的:用中链甘油三酯(MCT)替代长链甘油三酯(LCT)可减轻酒精性肝损伤。由于酒精性肝损伤和非酒精性脂肪性肝炎(NASH)的发病机制相似,我们的目的是评估MCT对NASH是否也有益。

方法

我们使用了一种大鼠NASH模型,其中玉米油(占总热量的35%)被等热量的MCT替代。

结果

部分替代LCT并未改善肝脏脂肪堆积、4-羟基壬烯醛、I型胶原蛋白及其mRNA水平,但增加了肿瘤坏死因子-α(TNF-α)及其mRNA水平(p<0.001)。然而,在给予高脂饮食量限制为正常摄入量2/3的大鼠中,无论有无MCT,这些不良反应均有所减轻,包括肝脏脂肪变性减轻和甘油三酯水平降低,但MCT并无有益作用。当70%的脂肪热量被MCT替代且饮食中不再含有LCT时,未发生脂肪变性且肝脏TNF-α水平较低。当所有MCT与碳水化合物一起给予(而非LCT)时,肝脏TNF-α水平也降低(p<0.001)。

结论

只要饮食中不含大量LCT,MCT就无肝毒性。随意喂食时用MCT完全替代饮食中的LCT是有益的,而部分替代则会产生肝毒性,除非限制饮食摄入量。

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