罗格列酮对db/db小鼠脂肪组织锌alpha2糖蛋白及线粒体生物合成相关因子表达的影响  

Effects of Rosiglitazone on expression of Zinc-alpha 2-glycoprotein and mitochondrial biogenesis related factors in adipose tissue

作　　者：肖新华[1] 李芬[1] 冉莉[1] 周峻林[1] 李菡[1] 杨靖[1] 刘江华[1] 文格波[1] 

机构地区：[1]南华大学附属第一医院内分泌科,湖南衡阳421001

出　　处：《中国现代医学杂志》2013年第29期1-7,共7页China Journal of Modern Medicine

基　　金：国家自然科学基金(No:81070667);教育部重点项目(No:211125);湖南省教育厅青年基金(No:10B092)

摘　　要：目的探讨罗格列酮对db/db小鼠脂肪组织锌alpha2糖蛋白及线粒体生物合成相关因子表达的影响。方法 8周龄SPF级雄性db/db小鼠28只,随机分为糖尿病模型组和罗格列酮干预组,每组14只。8周龄SPF级雄性db/m小鼠作为对照。干预组予以罗格列酮10 mg/(kg·d)灌胃4周和8周,其余各组予以等体积生理盐水灌胃。测定血清游离脂肪酸(FFA)、三酰甘油(TG)及总胆固醇(TC)含量。应用RT-PCR及Western blotting方法检测内脏脂肪组织锌alpha2糖蛋白及线粒体生物合成相关因子的mRNA和蛋白表达。留取部分新鲜脂肪组织置于10%甲醛溶液HE染色,光镜观察脂肪细胞形态。结果自发性糖尿病db/db小鼠的摄食量、饮水量、体质量增加值、内脏脂肪量、体脂比、血清空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG)、游离脂肪酸(FFA)水平均明显高于非糖尿病db/m小鼠(P<0.05)。脂肪细胞体积明显大于非糖尿病db/m小鼠,脂肪组织ZAG及线粒体生物合成相关因子PGC-1α、NRF-1、NRF-2、mtTFA mRNA和蛋白的表达均明显低于非糖尿病db/m小鼠(P<0.05)。罗格列酮干预db/db小鼠4周或8周后除血清TC水平无明显变化外,上述其他指标均有不同程度改善(P<0.05)。结论罗格列酮可改善db/db小鼠的糖脂代谢,且能够通过上调ZAG及线粒体生物合成相关因子PGC-1α、NRF-1、NRF-2、mtTFA的mRNA和蛋白表达,减少内脏脂肪积聚。[Objective ] To explore the effects of Rosiglitazone on expression of Zinc-alpha 2-glycoprotein and mitochondrial biogenesis related factors in adipose tissue of db/db mice. [Methods] Male db/db mice and their non-diabetic controls （db/＋m） were obtained from Nation Resource Center for Mutant Mice Model Animal Research Center （MARC）. All mice were used for experiments at 8 weeks of age after 1 week of ac- climation period. The animals were divided into experimental groups matched for both body weights and blood glucose levels. The db/db mice （n =28） and control db/m mice （n =14） received normal mouse chow. For the db/db model, mice received Rosiglitazone [10 mg/（kg＇min）] by oral gavage daily for either 4 or 8 week. The body weight, plasma glucose level, plasma lipid profile and FFA were assessed after treatment. Reverse tran- scriptase polymerase chain reaction （RT-PCR） and Western-blotting were used to detect the mRNA and prorein expression of ZAG and mitochondria biogenesis related genes, such as peroxisome proliferation receptor gamma assisted activating factor 1 alpha （PGC-1α）, nuclear respiratory factor 1/2 （NRF-1/2） and mitochondri- al transcription factor A （mtTFA）. The visceral adipose tissue section were stained with H＆E. [Results] The amount of food and water, weight gain, visceral fat mass, body fat ratio, fasting blood glucose, cholesterol, triglyceride, free fatty acids were significantly higher in spontaneous diabetes mellitus （db/db） mice than non diabetic （db/m） mice. In db/db mice, the expression levels of ZAG and mitochondrial biogenesis related factors （PGC-1α, NRF-1/2, mtTFA） were significantly lower than the non diabetic mice. After treatment with Rosiglitazone, the size of adipocytes were significant smaller and expression of ZAG and mitochondrial biogen- esis related factors were significant improved compared with control db/db mice. [Conclusion] Rosiglitazone reduces fat accumulation, particularly in the visceral compartment, improves

关 键 词：DB db小鼠 罗格列酮 锌alpha2糖蛋白 线粒体生物合成 

分 类 号：R-332[医药卫生] R587.1