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铁预负荷通过增加凋亡性细胞死亡加重大鼠营养性脂肪性肝炎。

Iron preloading aggravates nutritional steatohepatitis in rats by increasing apoptotic cell death.

作者信息

Imeryuz Nese, Tahan Veysel, Sonsuz Abdullah, Eren Fatih, Uraz Suleyman, Yuksel Meral, Akpulat Sertac, Ozcelik Dervis, Haklar Goncagul, Celikel Cigdem, Avsar Erol, Tozun Nurdan

机构信息

Department of Gastroenterology, Marmara University School of Medicine, Altunizade, Istanbul, Turkey.

出版信息

J Hepatol. 2007 Dec;47(6):851-9. doi: 10.1016/j.jhep.2007.06.018. Epub 2007 Aug 13.

DOI:10.1016/j.jhep.2007.06.018
PMID:17825453
Abstract

BACKGROUND/AIMS: High serum ferritin and liver iron concentrations were found in some patients with NASH, suggesting a role for iron as a co-factor that aggravates liver injury. The aim of this study is to investigate the effects of parenteral iron in a rat model of NASH induced by a methionine choline deficient diet (MCDD).

METHODS

Wistar rats were divided into 1 - Control, 2 - Iron (Fe), 3 - MCDD, 4 - MCDD&Fe groups. Iron dextran 100mg/kg was administered intra-muscularly in groups 2 and 4. All rats were fed MCDD, Groups 1 and 2 were supplied with choline and methionine. Blood and tissue samples were obtained after 4weeks.

RESULTS

The iron injection alone did not affect the liver whereas MCDD led to steatohepatitis. Iron worsened steatosis without any obvious effect on accompanying inflammation. It aggravated tissue injury by increasing apoptosis. Liver fibrosis was observed only in 3 out of 10 rats in the MCDD&Fe group.

CONCLUSIONS

Observation of liver fibrosis only in the MCDD&Fe group suggests that iron induced increase in apoptosis contributes to the development of fibrosis at an earlier time than expected.

摘要

背景/目的:在一些非酒精性脂肪性肝炎(NASH)患者中发现血清铁蛋白和肝脏铁浓度较高,提示铁作为一种辅助因子在加重肝损伤中发挥作用。本研究的目的是探讨胃肠外铁剂对蛋氨酸胆碱缺乏饮食(MCDD)诱导的NASH大鼠模型的影响。

方法

将Wistar大鼠分为1 - 对照组、2 - 铁剂组(Fe)、3 - MCDD组、4 - MCDD&Fe组。第2组和第4组大鼠肌肉注射100mg/kg右旋糖酐铁。所有大鼠均给予MCDD饮食,第1组和第2组补充胆碱和蛋氨酸。4周后采集血液和组织样本。

结果

单独注射铁剂对肝脏无影响,而MCDD可导致脂肪性肝炎。铁剂加重了脂肪变性,对伴随的炎症无明显影响。铁剂通过增加细胞凋亡加重组织损伤。仅在MCDD&Fe组的10只大鼠中有3只观察到肝纤维化。

结论

仅在MCDD&Fe组观察到肝纤维化,提示铁诱导的细胞凋亡增加比预期更早地促进了纤维化的发展。

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