高果糖喂养大鼠致脂肪肝的机制及非诺贝特的干预作用  

Mechanism of fatty liver induced by high-fructose-feeding in rats and intervention effect of fenofibrate

作　　者：李洋[1] 高哲[2] 任路平[3,2] 张璞[1] 宋光耀[2] LI Yang;GAO Zhe;REN Luping;ZHANG Pu;SONG Guangyao(School of Graduate,Hebei Medical University,Shijiazhuang 050017,China)

机构地区：[1]河北医科大学研究生院,石家庄市050017 [2]河北省人民医院内分泌科,石家庄市050051 [3]河北医科大学内科学教研室,石家庄市050017

出　　处：《实用医学杂志》2017年第14期2287-2290,共4页The Journal of Practical Medicine

基　　金：河北省自然科学基金项目(编号:H2015307034)

摘　　要：目的观察高果糖饮食诱导大鼠脂肪肝的机制及非诺贝特的干预作用。方法雄性Wistar大鼠随机分为对照组、高果糖组和非诺贝特组[高果糖喂养第8周后给予非诺贝特30 mg/(kg·d)],喂养12周后处死大鼠并测定各组大鼠血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、总胆固醇(TC)、游离甘油三酯(TG)及肝脏TG含量;测定脂肪酸合酶(Fas)、内质网应激相关蛋白免疫球蛋白重链结合蛋白(Bip)的表达,自噬相关蛋白自噬相关基因(Atg7)、酵母自噬相关蛋白6同系物(beclin1)、自噬标记轻链蛋白3(LC3)及自噬相关通路哺乳动物雷帕霉素靶蛋白(m TOR)蛋白表达。结果与对照组和非诺贝特组相比,高果糖组的血AST、血TC、血游离TG及肝TG均显著增高(均P<0.01)。与对照组和非诺贝特组比较,高果糖组大鼠的肝内Fas、Bip、m TOR表达增加,Atg7、beclin1、LC3表达降低。结论长期高果糖喂养引起大鼠肝脏脂质沉积及肝细胞损伤,并伴有肝脏内质网应激及自噬改变,非诺贝特治疗可改善高果糖饮食诱导的脂肪肝和肝细胞损伤,其机制可能与非诺贝特影响Fas并改善肝脏内质网应激及自噬有关。Objective To observe the effect of fenofibrate intervention on high?fructose?feeding?induced liver steatosis in rats and explore the possible mechanism.Methods Male Wistar rats were randomly divided into control group,high fructose group and fenofibrate group[fenofibrate intervention started after8weeks of high fructose feeding,30mg/(kg·d)].Rats were sacrificed after12?week of high fructose feeding.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),free triglyceride(TG)and liver TG content were determined;protein levels of fatty acid synthase(FAS),endoplasmic reticulum stress marker Bip and autophagy markers such as Atg7,Beclin1,LC3and the related pathway mTOR in liver tissues were detected.Results Compared with those in control group and fenofibrate group,serum AST,serum total cholesterol,blood free TG and hepatic TG were significantly increased in high?fructose group(P<0.01).The protein expression of Fas,Bip and mTOR were significantly increased in high?fructose group compared with those in control group and fenofibrate group;the protein expression of Atg7,beclin1and LC3were significantly decreased in highfructose group compared with those in control group and fenofibrate group.Conclusions Long?term high?fructosefeeding induces fatty liver and liver cell injury,and may affect ERS and autophagy.High?fructose?feeding?induced fatty liver may be improved by fenofibrate and its underlying mechanism might be associated with Fas,ERS and autophagy in liver.

关 键 词：脂肪肝 非诺贝特 脂肪酸合酶 自噬 内质网应激 

分 类 号：R575[医药卫生—消化系统]