ob／ob肥胖小鼠肝脏炎症及能量代谢相关转录因子表达特征  

Characteristics of expression of energy metabolism-related transcription factors in the liver of ob/ob mice

作　　者：崔欢欢[1] 李继斌[2] 柴水琴 明月[1] 王冬娟[3] 彭川[2] 刘丹[3] 肖晓秋[1] 

机构地区：[1]重庆医科大学附属第一医院脂糖代谢实验室,重庆400016 [2]重庆医科大学公共卫生与管理学院营养与卫生学教研室,重庆400016 [3]重庆医科大学附属儿童医院、儿童发育疾病研究省部共建教育部重点实验室,重庆400014

出　　处：《重庆医科大学学报》2014年第7期915-918,共4页Journal of Chongqing Medical University

基　　金：国家自然科学基金重点资助项目(编号:81030008);国家自然科学基金面上资助项目(编号:81270947)

摘　　要：目的:以ob/ob基因敲除肥胖小鼠为研究模型,探讨肥胖对小鼠肝脏炎症的影响以及ob/ob小鼠肝脏中与能量代谢相关转录因子:过氧化物酶体增殖物激活受体γ共激活因子-1α(peroxisome proliferator activated receptorγcoactivator-1α,PGC-1α)、过氧化物酶体增殖物激活受体α(peroxisome proliferator activated receptorα,PPARα)、核呼吸因子1(nuclear respiratory factor 1,NRF1)的基因表达特征。方法:选取以C57BL/6J为背景的雄性ob/ob肥胖小鼠(以下简称ob/ob小鼠)作为肥胖模型,同龄正常C57BL/6J雄性小鼠作为对照,2组小鼠各8只,于SPF级动物房饲养至5月龄,处死后取肝组织,石蜡包埋切片,HE染色观察组织形态;抗原F4/80免疫组化染色观察巨噬细胞浸润情况;RT-PCR检测各转录因子mRNA表达水平。结果:5月龄ob/ob小鼠体质量和肝脏质量高于对照组(t=9.66,P=0.000;t=9.98,P=0.000);石蜡切片HE染色结果显示ob/ob小鼠肝细胞胞浆内出现空泡状脂肪滴;F4/80免疫组化结果显示ob/ob小鼠肝脏组织巨噬细胞浸润明显;RT-PCR结果显示ob/ob小鼠肝脏组织转录因子PGC-1α、PPARα、NRF1的mRNA表达水平较对照组明显上调(t=3.02,P=0.009;t=5.64,P=0.000;t=2.93,P=0.011)。结论:ob/ob小鼠表现出显著的肥胖特征,肝细胞出现明显脂质沉积,肝组织炎性细胞浸润;上述改变可能与肝脏能量代谢相关转录因子PGC-1α,PPARα和NRF1的表达增加有关。Objective：To examine the mRNA expression characteristics of hepatic energy metabolism-related transcription factors： peroxisome proliferator activated receptor γ, coactivator- 1 α （PGC- lα）, peroxisome proliferator activated receptor ot （PPARα） and nuclear respiratory factor I（NRF1） in ob/ob mice. Methods：Male ob/ob obese mice on a C57BL/6J genetic background were used as obese model（n=8） and normal male C56BL/6J mice as control（n=8）. At the age of 5 months,liver samples were obtained after sacri- ficing. Liver morphologic analysis was performed by HE staining and macrohoages were stained by immunohistochmistry method us- ing F4/80 antibody. RT-PCR was performed to determine the mRNA expression levels of interested genes. Results： Both body weight and liver weight of the ob/ob mice were higher than those of control group（t=9.66,P=0.000;t=9.98,P=0.000）. In the ob/ob group, HE showed lipid accumulation. Immunohistochmistry staining for F4/80 results showed more severe inflammatory cell infiltration in ob/ ob group. Compared with those in control group,PGC-lα,PPARα,NRF1 mRNA expression levels increased significantly（t=3.02, P=0.009;t=5.64,P=0.000;t=2.93,P=-0.011）. Conclusion：The ob/ob mice are obese than normal controls. There are significant hepatic lipid accumulation and inflammatory cell infiltration in the livers of ob/ob mice. which may related with the increased expressions of PGC-lα,PPARα and NRF1.

关 键 词：ob ob小鼠 脂肪肝 炎症 过氧化酶体增殖物激活受体γ共激活因子-1α 过氧化物酶体增殖物激活受体or 核呼吸因 子1 

分 类 号：R333.4[医药卫生—人体生理学]