Pentoxifylline attenuates methionine- and choline-deficient-diet-induced steatohepatitis by suppressing TNF-α expression and endoplasmic reticulum stress.

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-01-29 DOI:10.1155/2012/762565
Min Kyung Chae, Sang Gyu Park, Sun-Ok Song, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee, Byung-Wan Lee
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引用次数: 22

Abstract

Background: Pentoxifylline (PTX) anti-TNF properties are known to exert hepatoprotective effects in various liver injury models. The aim of this study was to investigate whether PTX has beneficial roles in the development of methionine- and choline-deficient-(MCD-) diet-induced NAFLD SD rats in vivo and TNF-α-induced Hep3B cells in vitro.

Methods: SD Rats were classified according to diet (chow or MCD diet) and treatment (normal saline or PTX injection) over a period of 4 weeks: group I (chow + saline, n = 4), group II (chow + PTX), group III (MCD + saline), and group IV (MCD + PTX). Hep3B cells were treated with 100 ng/ml TNF-α (24 h) in the absence or presence of PTX (1 mM).

Results: PTX attenuated MCD-diet-induced serum ALT levels and hepatic steatosis. In real-time PCR and western blotting analysis, PTX decreased MCD-diet-induced TNF-alpha mRNA expression and proapoptotic unfolded protein response by ER stress (GRP78, p-eIF2, ATF4, IRE1α, CHOP, and p-JNK activation) in vivo. PTX (1 mM) reduced TNF-α-induced activation of GRP78, p-eIF2, ATF4, IRE1α, and CHOP in vitro.

Conclusion: PTX has beneficial roles in the development of MCD-diet-induced steatohepatitis through partial suppression of TNF-α and ER stress.

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己酮茶碱通过抑制TNF-α表达和内质网应激,减轻蛋氨酸和胆碱缺乏饮食引起的脂肪性肝炎。
背景:己酮茶碱(PTX)抗tnf的特性在各种肝损伤模型中发挥肝保护作用。本研究的目的是探讨PTX是否在体内蛋氨酸和胆碱缺乏(MCD-)饮食诱导的NAFLD SD大鼠和TNF-α-诱导的Hep3B细胞的发展中具有有益作用。方法:SD大鼠按饮食(鼠粮或MCD饮食)和治疗(生理盐水或PTX注射)4周分为I组(鼠粮+生理盐水,n = 4)、II组(鼠粮+ PTX)、III组(MCD +生理盐水)和IV组(MCD + PTX)。Hep3B细胞用100 ng/ml TNF-α (24 h)处理,不管PTX是否存在(1 mM)。结果:PTX减轻mcd饮食诱导的血清ALT水平和肝脂肪变性。real-time PCR和western blotting分析显示,PTX在体内降低mcd饮食诱导的tnf - α mRNA表达和内质网应激(GRP78、p-eIF2、ATF4、IRE1α、CHOP和p-JNK活化)对促凋亡未折叠蛋白的反应。PTX (1 mM)在体外降低TNF-α-诱导的GRP78、p-eIF2、ATF4、IRE1α和CHOP的活化。结论:PTX通过部分抑制TNF-α和内质网应激在mcd饮食诱导的脂肪性肝炎的发展中具有有益作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Experimental Diabetes Research
Experimental Diabetes Research 医学-内分泌学与代谢
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审稿时长
3-8 weeks
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