高果糖喂养大鼠致脂肪肝的机制及非诺贝特的干预作用

发布时间：2019-08-19 12:50

【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P0.01)。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。
[Abstract]:Objective to observe the mechanism of fatty liver induced by high fructose diet and the intervention effect of fenofibrate. Methods male Wistar rats were randomly divided into control group, high fructose group and fenofibrate group [treated with fenofibrate 30 mg/ (kg 路d) after 8 weeks of high fructose feeding]. After 12 weeks of feeding, the rats were killed and the contents of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), free glycerol (TG) and liver TG in each group were measured. The expression of immunoglobulin heavy chain binding protein (Bip), autophagy related protein autophagy related gene (Atg7), yeast autophagy associated protein 6 homologue (beclin1), autophagy labeled light chain protein 3 (LC3) and rapamicin target protein (m TOR) protein in autophagy related pathway mammals were measured. Results compared with the control group and fenofibrate group, the blood AST, blood TC, free TG and liver TG in the high fructose group were significantly higher than those in the control group and fenofibrate group (all P 0.01). Compared with the control group and fenofibrate group, the expression of Fas,Bip,m TOR in the liver of rats with high fructose increased and the expression of Atg7,beclin1,LC3 decreased. Conclusion long-term high fructose feeding can induce liver lipid deposition and hepatocytes injury, accompanied by endoplasmic reticulum stress and autophagy. Fenofibrate can improve fatty liver and hepatocytes injury induced by high fructose diet. The mechanism may be related to fenofibrate affecting Fas and improving endoplasmic reticulum stress and autophagy.
【作者单位】：河北医科大学研究生院;河北省人民医院内分泌科;河北医科大学内科学教研室;
【基金】：河北省自然科学基金项目(编号:H2015307034)
【分类号】：R575

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