不同品系小鼠肥胖模型比较及C57BL/6J小鼠肥胖机制研究  

Comparison of obesity models established in the different strains of mice and the mechanism of obese C57BL/6J mice

作　　者：刘芳[1] 高南南[1] 杨润梅[1] 冀敏[1] 初欣欣 康卓颖 

机构地区：[1]中国医学科学院北京协和医学院药用植物研究所药理毒理研究中心,北京100193

出　　处：《中国药理学通报》2013年第3期360-365,共6页Chinese Pharmacological Bulletin

基　　金：北京市自然科学基金资助项目(No 7122112)

摘　　要：目的建立和比较不同品系小鼠肥胖模型,并研究C57BL/6J小鼠肥胖形成的分子机制。方法选用C57BL/6J、ICR和KM 3个品系♂小鼠,各品系小鼠随机分为正常对照和高脂模型组,分别在饲养4周与8周后测定小鼠体重、脂肪重量、Lee’s指数;脂肪细胞形态学观察和横截面面积计量;酶法检测血脂和LPL活性,应用荧光实时定量PCR技术探讨模型形成分子机制。结果 C57BL/6J小鼠模型组体重、脂肪重量、Lee’s指数、脂肪细胞横截面面积与对照组比较均明显升高,形成良好肥胖模型,而ICR和KM小鼠肥胖指标不如C57BL/6J小鼠变化明显。机制研究表明,C57BL/6J小鼠造模后血清LPL活性升高,肝脏PPARα、脂肪组织PPARγ和DGAT表达上调,脂肪组织HSL、ATGL和TGH表达下调,这些酶、受体的表达变化是形成肥胖的重要机制。结论 C57BL/6J小鼠经高脂饲料诱导4周后可形成良好肥胖模型,PPARα、PPARγ、LPL、DGAT、HSL、ATGL和TGH既是肥胖形成的主要机制,也是减肥药物作用靶点判断的生物标志物。Aim To establish and compare different strains of mouse obesity models and study the molecular mechanism of obesity formation in C57BL/6J mice.Methods The male mice from three different mouse strain C57BL/6J、ICR and KM were randomly divided in to the control group and the model group fed with high-fat diet.The body weight,fat weight,Lee＇s index,morphology observation and cross-sectional area of adipocytes were determined after 4 and 8 weeks.Serum lipids and LPL activity were detected by enzymatic method.The molecular mechanism was tested by real-time PCR.Results In comparison with the control group,the body weight,fat weight,Lee′s index and cross-sectional area of adipocytes in C57BL/6J mice significantly increased.These illustrated that the C57BL/6J mice could form a good obesity model.However,the obesity indexes of ICR and KM mice changed less than C57BL/6J mice.The mechanism research showed that the LPL activity increased in C57BL/6J mice fed with high-fat diet,and the hepatic PPARα and adipose PPARγ and DGAT mRNA expressions were up-regulated while adipose HSL,ATGL and TGH mRNA expressions were down-regulated.The alternation of these enzymes and receptors were the critical factors for obesity formation.Conclusion C57BL/6J mice fed with high fat diet for 4 weeks can form a good obesity model.PPARα,PPARγ,DGAT,HSL,ATGL and TGH are the main mechanisms of obesity formation,and also the biomarkers of antiobesity drugs targets.

关 键 词：C57BL 6J小鼠 ICR小鼠 KM小鼠 肥胖 LPL PPARα PPARγ DGAT HSL ATGL TGH 

分 类 号：R-332[医药卫生] R363-332