Fructose-induced fatty liver disease - Hepatic effects of blood pressure and plasma triglyceride reduction
Fructose-induced fatty liver disease - Hepatic effects of blood pressure and plasma triglyceride reduction
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DOI：
10.1161/01.hyp.0000164570.20420.67
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发表时间：
2005-05-01
期刊：
影响因子：
8.3
通讯作者：
Sela, BA
中科院分区：
文献类型：
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作者：
Ackerman, Z;Oron-Herman, M;Sela, BA
非酒精性脂肪性肝病（NAFLD）最常见的危险因素是代谢综合征。在这项研究中，我们描述了大鼠肝脏病理、肝脂质组成和肝铁浓度（HIC）的变化，这些变化发生在给予富含果糖的饮食（FED）的大鼠中，有或没有治疗性操作来降低血压和血浆甘油三酯。给大鼠喂食FED或标准鼠粮5周。服用FED的大鼠分为4组：最后2周服用氨氯地平（15 mg/kg /天）、卡托普利（90 mg/kg /天）、贝扎布特（10 mg/kg /天），对照组只服用FED。大鼠出现肝大泡和微泡脂肪沉积，肝甘油三酯（+198%）和肝胆固醇（+89%）升高，但肝磷脂（-36%）、高甘油三酯血症（+223%）和高血压（+15%）降低，HIC未升高。氨氯地平降低血压（-18%），血浆甘油三酯（-12%），但肝脏甘油三酯和磷脂浓度没有变化。卡托普利降低血压（-24%）、血浆甘油三酯（-36%）、肝脏甘油三酯（-51%）和肝大泡脂肪（-51%），但增加HIC(+23%)，肝纤维化增加。贝扎菲特降低血浆甘油三酯（-49%），肝脏甘油三酯（-78%），肝大泡脂肪（-90%）和血压（-11%）。我们认为FED大鼠可以作为人类NAFLD的合适模型。用于治疗代谢综合征各方面的药物可能对肝脏有影响。NAFLD大鼠HIC升高可能与肝纤维化增加有关。
The most known risk factor for nonalcoholic fatty liver disease (NAFLD) is the metabolic syndrome. In this study, we characterized changes in liver pathology, hepatic lipid composition, and hepatic iron concentration (HIC) occurring in rats given fructose-enriched diet ( FED), with and without therapeutic maneuvers to reduce blood pressure and plasma triglycerides. Rats were given FED or standard rat chow for 5 weeks. Rats on FED were divided into 4 groups: receiving amlodipine (15 mg/kg per day), captopril (90 mg/kg per day), bezafibrate (10 mg/kg per day) in the last 2 weeks, or a control group that received FED only. FED rats had hepatic macrovesicular and microvesicular fat deposits develop, with increase in hepatic triglycerides (+198%) and hepatic cholesterol (+89%), but a decrease in hepatic phospholipids (-36%), hypertriglyceridemia (+223%), and hypertension (+15%), without increase in HIC. Amlodipine reduced blood pressure (-18%), plasma triglycerides (-12%), but there was no change in hepatic triglycerides and phospholipids concentrations. Captopril reduced blood pressure (-24%), plasma triglycerides (-36%), hepatic triglycerides (-51%), and hepatic macrovesicular fat (-51%), but increased HIC (+23%), with a borderline increase in hepatic fibrosis. Bezafibrate reduced plasma triglycerides (-49%), hepatic triglycerides (-78%), hepatic macrovesicular fat (-90%), and blood pressure (-11%). We conclude that FED rats can be a suitable model for human NAFLD. Drugs administered to treat various aspects of the metabolic syndrome could have hepatic effects. An increase in HIC in rats with NAFLD could be associated with increased hepatic fibrosis.