SREBP-1c在白藜芦醇预防大鼠非酒精性脂肪肝发生中的作用  

SREBP-1c is involved in preventive effect of resveratrol on pathogenesis of nonalcoholic fatty liver disease in rats

作　　者：高燕翔[1] 张勇[1] 刘裕[1] 张乾勇[1] 糜漫天[1] 

机构地区：[1]第三军医大学军事预防医学院营养与食品安全研究中心,重庆市营养与食品安全重点实验室,重庆市医学营养研究中心,重庆400038

出　　处：《第三军医大学学报》2015年第17期1704-1708,共5页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81273059)~~

摘　　要：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(nonalcoholic fatty liver disease,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+50 mg/kg RSV组(每天50 mg/kg RSV,HFR50组)和高脂膳食+100 mg/kg RSV组(每天100 mg/kg RSV,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,Western blot检测p AMPK、SIRT1、SREBP-1c、FAS的蛋白表达以及实时定量PCR分析SREBP-1c和FAS mRNA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p AMPK蛋白表达降低(P<0.05)、SREBP-1c和FAS mRNA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p AMPK与SIRT1蛋白表达和下调SREBP-1c表达与转录活性,预防NAFLD的发生。Objective To investigate the role of sterol regulatory element binding protein-1c（ SREBP-1c） in preventive effect of resveratrol（ RSV） on the occurrence of nonalcoholic fatty liver disease（ NAFLD） in rats treated with high-fat diet. Methods Forty eight-week-old male SD rats were randomly divided into 4 groups： control group treated with normal diet,high-fat diet group treated with normal diet and lard,high-fat diet ＋ 50 mg / kg RSV group,and high-fat diet ＋ 100 mg / kg RSV group. During 8-week intervention,the body mass and food consumption were weighed weekly for each rat. After the intervention,the concentrations of total cholesterol（ TC） and triglyceride（ TG） in the serum and liver were measured. The hepatic steatosis was observed by histological staining with hematoxylin and eosin. The protein levels of p AMPK,SIRT1,SREBP-1c and FAS were determined by Western blotting,and the mRNA levels of SREBP-1c and FAS were measured by quantitative real-time PCR. Meanwhile,the binding degree of FAS promoter sequence SRE and SREBP-1c was analyzed by chromatin immunoprecipitation（ Ch IP） assay. Results RSV reduced the body mass of the high-fat fed rats（ P 0. 05）,but their daily energy intake had no obvious change. RSV significantly lowered TG levels in the serum and liver of the high-fat fed rats（ P 0. 05）. Highfat diet induced hepatic steatosis,and resulted in low protein expression of p AMPK and SIRT1 in the liver of the rats（ P 0. 05）,high mRNA and protein expression of SREBP-1c and FAS（ P 0. 05）,and high binding degree of SRE and SREBP-1c（ P 0. 05）,while RSV significantly inhibited these effects（ P 0. 05）.Conclusion RSV can prevent the occurrence of NAFLD in the high-fat fed rats through up-regulating p AMPK and SIRT1 and down-regulating SREBP-1c and transcriptional activity.

关 键 词：白藜芦醇 非酒精性脂肪肝 固醇调节元件结合蛋白-1C 

分 类 号：R151.3[医药卫生—营养与食品卫生学] R394.2[医药卫生—公共卫生与预防医学]