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金雀异黄素对高脂肪高蔗糖饮食诱导的大鼠肝脂肪变性有有益作用。

Genistein has beneficial effects on hepatic steatosis in high fat-high sucrose diet-treated rats.

机构信息

Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China.

Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China.

出版信息

Biomed Pharmacother. 2017 Jul;91:964-969. doi: 10.1016/j.biopha.2017.04.130. Epub 2017 May 13.

DOI:10.1016/j.biopha.2017.04.130
PMID:28514835
Abstract

Genistein, a kind of phytoestrogen abundant in soybeans, is beneficial for alleviating non-alcoholic fatty liver disease (NAFLD), but the specific mechanism was not clearly understood. This study was designed to determine the effect of genistein on NAFLD and explore the possible mechanism. 36 male Sprague-Dawley rats were divided into 4 groups: the control group, high fat-high sucrose diet (HFS) group, HFS with 4mg/kg body weight genistein, and HFS with 8mg/kg body weight genistein. 12 weeks later, serum and hepatic lipid profiles, liver histopathological examination were characterized. The protein levels of liver AMP-activated protein kinase (AMPK), phosphorylation of AMPK (p-AMPK), acetyl-CoA carboxylase (ACC), phosphorylation of ACC (p-ACC) and sterol regulatory element binding protein 1 (SREBP-1) were determined by western blot. mRNA expressions of fatty acid synthase gene (FAS) and glycerol-3-phosphate acyltransferase (GPAT), peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transfer enzyme-1 (CPT-1) and acyl-CoA oxidase (ACO) were measured by reverse transcription polymerase chain reaction (RT-PCR). Results showed that genistein effectively improved serum and hepatic lipid metabolism and diminished fat accumulation in liver. And the protein level of hepatic p-AMPK and p-ACC were increased, but SREBP-1 was decreased by genistein. Meanwhile, the mRNA levels of FAS and GPAT were lower, but PPARα, CPT-1, ACO were higher in rats treated with genistein compared with HFS group. Collectively, genistein can improve hepatic steatosis via activating AMPK, thus promoting fatty acid oxidation and inhibiting lipid synthesis in liver.

摘要

染料木黄酮是大豆中丰富的一种植物雌激素,有益于缓解非酒精性脂肪性肝病(NAFLD),但其具体机制尚不清楚。本研究旨在确定染料木黄酮对 NAFLD 的作用,并探讨其可能的机制。36 只雄性 Sprague-Dawley 大鼠随机分为 4 组:对照组、高脂肪高蔗糖饮食(HFS)组、HFS 加 4mg/kg 体重染料木黄酮组和 HFS 加 8mg/kg 体重染料木黄酮组。12 周后,检测血清和肝脂质谱,进行肝组织病理学检查。Western blot 法检测肝组织 AMP 激活蛋白激酶(AMPK)、磷酸化 AMPK(p-AMPK)、乙酰辅酶 A 羧化酶(ACC)、磷酸化 ACC(p-ACC)和固醇调节元件结合蛋白 1(SREBP-1)的蛋白水平。反转录聚合酶链反应(RT-PCR)法检测脂肪酸合成酶基因(FAS)和甘油-3-磷酸酰基转移酶(GPAT)、过氧化物酶体增殖物激活受体α(PPARα)、肉碱棕榈酰转移酶-1(CPT-1)和酰基辅酶 A 氧化酶(ACO)的 mRNA 表达。结果表明,染料木黄酮能有效改善血清和肝脂质代谢,减少肝脂肪堆积。染料木黄酮还能增加肝组织 p-AMPK 和 p-ACC 蛋白水平,降低 SREBP-1 蛋白水平。同时,与 HFS 组相比,染料木黄酮治疗组 FAS 和 GPAT 的 mRNA 水平降低,而 PPARα、CPT-1、ACO 的 mRNA 水平升高。综上,染料木黄酮通过激活 AMPK 改善肝脂肪变性,从而促进脂肪酸氧化,抑制肝脏脂质合成。

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