Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease
Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease
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DOI：
10.1111/j.1478-3231.2006.01329.x
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发表时间：
2006-12-01
影响因子：
6.7
通讯作者：
de la M Hall, Pauline
中科院分区：
文献类型：
--
作者：
Kirsch, Richard;Sijtsema, Helene P.;de la M Hall, Pauline
背景/目的：本研究旨在确定过量的肝铁是否会增强非酒精性脂肪性肝病（NAFLD）蛋氨酸胆碱缺乏（MCD）模型的肝损伤。研究方法：给铁负荷大鼠喂食MCD或对照饲料[MCD饲料加酒石酸氢胆碱（2 g/kg）和DL-蛋氨酸（3 g/kg）] 4周和12周，之后评价肝脏病理学、肝脏铁、甘油三酯、脂质过氧化产物和羟脯氨酸（HYP）水平以及血清丙氨酸氨基转移酶（ALT）水平。结果如下：MCD动物中的铁补充在4周和12周时导致肝脏铁过载的组织学证据，并且在12周时肝脏铁浓度增加14倍（P < 0.001）。在这些动物中补充铁与4周时小叶坏死性炎症增加（P < 0.02）和12周时肝脂肪变性（P <0.01）、肝甘油三酯水平（P < 0.01）、肝共轭二烯（CD; P < 0.02）和血清ALT水平（P < 0.002）降低相关。4周时，肝脏脂肪变性（P < 0.005）和CD（P < 0.01）明显减少。补铁与小静脉周围纤维化增加的趋势相关，而与肝HYP含量无关。结论：在NAFLD MCD模型中，肝脏铁过载与肝脏脂质降低、早期脂质过氧化产物减少、坏死性炎症增加和小静脉周围纤维化增加的趋势相关。
Background/aims: This study sought to determine whether excess hepatic iron potentiates liver injury in the methionine choline-deficient (MCD) model of non-alcoholic fatty liver disease (NAFLD). Methods: Iron-loaded rats were fed either MCD or control diets [MCD diet plus choline bitartrate (2 g/kg) and DL-methionine (3 g/kg)] for 4 and 12 weeks, after which liver pathology, hepatic iron, triglyceride, lipid peroxidation products and hydroxyproline (HYP) levels and serum alanine aminotransferase (ALT) levels were evaluated. Results: Iron supplementation in MCD animals resulted in histologic evidence of hepatic iron overload at 4 and 12 weeks and a 14-fold increase in hepatic iron concentration at 12 weeks (P < 0.001). Iron supplementation in these animals was associated with increased lobular necroinflammation at 4 weeks (P < 0.02) and decreased hepatic steatosis (P < 0.01), hepatic triglyceride levels (P < 0.01), hepatic-conjugated dienes (CD; P < 0.02) and serum ALT levels (P < 0.002) at 12 weeks. Reduced hepatic steatosis (P < 0.005) and CD (P < 0.01) were apparent by 4 weeks. Iron supplementation was associated with a trend towards increased perivenular fibrosis not hepatic HYP content. Conclusions: Hepatic iron overload in the MCD model of NAFLD is associated with decreased hepatic lipid, decreased early lipid peroxidation products, increased necroinflammation and a trend towards increased perivenular fibrosis.