乳清酸诱导大鼠脂肪肝的机制研究  

MECHANISM OF OROTIC ACID-INDUCED FATTY LIVER IN RATS

作　　者：王玉明[1] 胡晓倩[1] 任兵兴[1] 王静凤[1] 薛长湖[1] 

机构地区：[1]中国海洋大学食品科学与工程学院,山东青岛266003

出　　处：《营养学报》2009年第4期330-333,338,共5页Acta Nutrimenta Sinica

基　　金：国家自然科学基金(No.30471319);新世纪优秀人才支持计划(No.NCET-04-0642)

摘　　要：目的研究乳清酸诱发大鼠脂肪肝的机制。方法将大鼠分成两组,对照组喂食AIN93标准饲料,模型组饲料中添加1%乳清酸。饲喂10d后,分别测定大鼠血清总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-C)含量,以及肝脏TC、TG、磷脂含量。同时测定了肝脏中脂肪酸合成酶(FAS)、肉碱棕榈酰转移酶(CPT)、微粒体甘油三酯转运蛋白(MTP)的活性和其mRNA表达量,以及固醇调节元件结合蛋白(SREBP-1c)和过氧化物酶体增殖物激活受体(PPARα)的mRNA表达量。结果乳清酸可显著提高大鼠血清TG浓度和肝脏TC、TG含量。添加乳清酸后,大鼠肝脏中FAS活性及mRNA水平明显上调,而CPT、MPT活性及mRNA水平明显下调,同时作为转录调节因子的SREBP-1cmRNA表达量增加3.13倍,PPARα mRNA表达量无明显变化。结论1%乳清酸诱发大鼠脂肪肝与SREBP-1c的表达量升高引发的脂肪合成亢进有关,并与脂肪酸氧化分解受抑制及MTP活性和基因表达量降低有关。Objective To investigate the mechanism of orotic acid-induced fatty liver in rats. Method Rats were randomly divided into 2 groups, and fed AIN93 diet with or without 1% orotic acid （OA） for 10d. Serum total cholesterol （TC）, triglyceride （TG）, high density lipoprotein-cholesterol （HDL-C）, hepatic lipids concentrations （TG, TC and phospholipids）, hepatic enzymes activities and mRNA levels of key enzymes related to lipids metabolism, as well as hepatic genes expression of transcription factors were determined. Results OA administration significantly increased serum and hepatic TG concentration. The activity and mRNA level of fatty acid synthase （FAS） were obviously up-regulated by OA treatment, whereas the activities and mRNA concentrations of carnitin palmitoyl transferase （CPT） and microsomal triglyceride transfer protein （MTP） were depressed significantly. Furthermore, OA also stimulated the mRNA expression of sterol regulatory element binding protein-1c （SREBP-1c）, but did not alter the mRNA concentrations of peroxisome proliferator-activated receptor alpha （PPARα） in liver. Conclusion： The stimulation of TG synthesis caused by enhancement of SREBP-1c and its target genes-FAS, which could be responsible for development of fatty liver. On the other hand, the inhibition of fatty acid beta-oxidation and VLDL secretion were related to the observed lipids accumulation.

关 键 词：乳清酸 脂肪肝 脂肪酸合成酶 微粒体甘油三酯转运蛋白 过氧化物酶体增殖物激活受体 

分 类 号：R575.5[医药卫生—消化系统]