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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 study the mechanism of orotic acid induced fatty liver in rats. Methods The rats were divided into two groups. The control group was fed AIN93 standard diet, and the model group was fed with 1% orotic acid. After being fed for 10 days, the levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) TG, phospholipid content. The activities of fatty acid synthase (FAS), carnitine palmitoyltransferase (CPT), microsomal triglyceride transporter (MTP) and their mRNA expression in the liver were also determined. The sterol regulatory element binding protein (SREBP- 1c) and peroxisome proliferator-activated receptor (PPARα) mRNA expression levels. Results orotic acid can significantly increase serum TG concentration and liver TC, TG content. After addition of orotate, the activity and mRNA level of FAS in rat liver were significantly increased, but the activity and mRNA level of CPT, MPT were significantly down-regulated, while the expression of SREBP-1 mRNA as a transcriptional regulator increased by 3.13-fold and the expression of PPARα mRNA was not significant Variety. Conclusions 1% orotate-induced fatty liver in rats is related to the hypertrophy induced by increased expression of SREBP-1c and is related to the inhibition of fatty acid oxidation and decomposition and the decrease of MTP activity and gene expression.