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脂肪肝小鼠的肝脏脂质代谢相关基因表达特征分析
陈榕1,2△,曹怡1,2△,周露婷2,麻献华2,王燕2,张海2,章卫平2*,邹大进1*
0
(1. 第二军医大学长海医院内分泌科,上海 200433
2. 第二军医大学基础部病理生理学教研室,上海 200433
共同第一作者
*通信作者)
摘要:
目的 分析ob/ob肥胖小鼠脂肪肝中脂质代谢相关基因的表达特征。方法 18周龄雄性ob/ob及其同窝对照小鼠各4只,禁食16 h后处死。检测小鼠体质量、肝脏湿质量/体质量、肝脏三酰甘油(TG)水平;用H-E和油红O染色观察肝脏的形态结构和脂质沉积情况;用实时荧光定量PCR方法检测肝脏脂质代谢相关基因的mRNA表达情况。结果 Ob/ob小鼠体质量、肝脏湿质量/体质量和肝脏组织TG水平均高于对照小鼠(P<0.05),H-E和油红O染色显示ob/ob小鼠发生肝脏脂质沉积;肝脏脂肪酸转位酶(CD36)、脂肪酸结合蛋白1(FABP1)、脂肪酸合酶(FASN)、乙酰辅酶A羧化酶1(ACC1)、极长链脂肪酸延长酶6(ELOVL6)和硬脂酰辅酶A去饱和酶1(SCD1)等mRNA表达水平在ob/ob小鼠肝脏均高于对照小鼠(P<0.05),而过氧化物酶体增殖剂激活受体α(PPARα)、软脂酸辅酶A氧化酶1(ACOX1)、载脂蛋白B (ApoB)和微粒体TG转移蛋白(MTP) mRNA在两组小鼠肝脏中的mRNA表达水平差异无统计学意义。结论 Ob/ob小鼠肝脏的脂肪酸摄取和从头合成相关基因的mRNA表达水平升高,而脂肪酸氧化及脂质向肝外转运的相关基因的mRNA表达水平无明显改变。
关键词:  非酒精性脂肪肝  肥胖  脂代谢障碍  基因表达
DOI:10.3724/SP.J.1008.2012.001051
投稿时间:2012-03-12修订日期:2012-05-16
基金项目:国家自然科学基金青年基金(81100614).
Characterization of lipid metabolism-related genes in mouse fatty liver
CHEN Rong1,2△,CAO Yi1,2△,ZHOU Lu-ting2,MA Xian-hua2,WANG Yan2,ZHANG Hai2,ZHANG Wei-ping2*,ZOU Da-jin1*
(1. Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
2. Department of Pathophysiology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China
Co-first authors.
*Corresponding authors.)
Abstract:
ObjectiveTo characterize the expression of lipid metabolism-related genes in the fatty liver of obese ob/ob mice. MethodsFour 18-weeks old male ob/ob and 4 control mice were sacrificed after 16 h fasting. Their body mass, ratio of liver wet mass to body mass and liver triglyceride contents were examined. H-E staining and Oil red O staining were performed to observe the histological changes and lipid deposition of the liver. Real-time quantitative RT-PCR was used to detect mRNA expression of lipid metabolism-related genes in the liver. ResultsThe body mass, ratio of liver wet mass to body mass and liver triglyceride contents were significantly higher in ob/ob mice than those in control mice (P<0.05). H-E staining and Oil red O staining showed severe hepatic steatosis in the ob/ob mice. The mRNA levels of fatty acid translocase (CD36), fatty acid binding protein 1 (FABP1), fatty acid synthase (FASN), acetyl-CoA carboxylase 1(ACC 1), elongation of very long chain fatty acids family member 6 (ELOVL6) and stearoyl-CoA desaturase 1 (SCD1) were significantly higher in ob/ob mice than those in control mice (P<0.05); and there were no significant differences in the mRNA levels of peroxisome proliferator-activated receptor α(PPARα), palmitoyl-CoA oxidase (ACOX1), apoprotein B (ApoB) or microsomal triglyceride transfer protein (MTP) between the two groups (P>0.05).ConclusionThe genes closely related to fatty acid uptake and de novo fatty acid synthesis are up-regulated in ob/ob liver, and those related to fatty acid oxidation and lipid transportation and VLDL secretion are not greatly affected at mRNA level.
Key words:  nonalcoholic fatty liver  obesity  lipid metabolism disorders  gene expression