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SREBP-1c在白藜芦醇预防大鼠非酒精性脂肪肝发生中的作用

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Keywords: 白藜芦醇,非酒精性脂肪肝,固醇调节元件结合蛋白-c

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Abstract:

目的探讨固醇调节元件结合蛋白-1c(SREBP-1c)在白藜芦醇(resveratrol,RSV)预防大鼠通过高脂膳食形成非酒精性脂肪肝(nonalcoholicfattyliverdisease,NAFLD)过程中的作用。方法40只8周龄雄性SD大鼠按随机数字表法分为4组:对照组(基础饲料,Con组)、高脂膳食组(基础饲料+猪油,HF组),高脂膳食+50mg/kgRSV组(每天50mg/kgRSV,HFR50组)和高脂膳食+100mg/kgRSV组(每天100mg/kgRSV,HFR100组)。干预8周,每周称量动物体质量和食物消耗量,干预后检测血清和肝脏中脂质含量,肝脏组织HE染色观察脂肪变性情况,Westernblot检测pAMPK、SIRT1、SREBP-1c、FAS的蛋白表达以及实时定量PCR分析SREBP-1c和FASmRNA表达,染色质免疫共沉淀法分析FAS启动子序列SRE与SREBP-1c的结合程度。结果白藜芦醇在不影响日常能量摄入的情况下能减少高脂喂养大鼠的体质量(P<0.05);白藜芦醇显著降低高脂喂养大鼠血清和肝脏中TG含量(P<0.05);高脂喂养诱导大鼠肝脂肪变性,导致大鼠的肝内SIRT1和pAMPK蛋白表达降低(P<0.05)、SREBP-1c和FASmRNA及蛋白表达升高(P<0.05)、FAS启动子SRE与SREBP-1c的结合程度增加(P<0.05),而白藜芦醇的干预能显著抑制上述效应(P<0.05)。结论白藜芦醇通过上调高脂喂养大鼠肝内pAMPK与SIRT1蛋白表达和下调SREBP-1c表达与转录活性,预防NAFLD的发生。

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