二甲双胍对肥胖大鼠骨骼肌脂肪异位沉积的干预作用  

Effects of metformin on skeletal muscle fatty ectopic deposition in high-fat induced obese rats

作　　者：夏同佳[1] 王佑民[1,2] 

机构地区：[1]安徽医科大学内分泌与代谢病研究所,合肥230032 [2]安徽医科大学第一附属医院内分泌科,合肥230022

出　　处：《安徽医科大学学报》2013年第3期236-240,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽高校省级自然科学研究基金(编号:KJ2011A161)

摘　　要：目的观察二甲双胍对高脂饲料诱导的SD肥胖大鼠骨骼肌组织中脂肪异位沉积和骨骼肌细胞膜脂肪酸转运蛋白(FAT/CD36)表达的干预作用。方法选用4周龄雄性SD大鼠50只,随机分为普通饮食对照组(NC组,n=14)和高脂饮食组(HF组,n=36)。HF组喂养12周高脂饲料,筛选出成功建立肥胖大鼠模型32只,再随机分为肥胖模型组(OB组,n=12)、二甲双胍高剂量组(H-Met组,n=10)和二甲双胍低剂量组(L-Met,n=10),干预期间3组继续给予高脂饮食。H-Met和L-Met组分别以200、100 mg/(kg.d)的二甲双胍灌胃,6周后空腹取血进行相关代谢指标测定;取骨骼肌组织检测肌束间甘油三酯(TG)含量,油红O染色了解脂肪异位沉积程度,免疫荧光染色检测骨骼肌FAT/CD36蛋白表达。结果 OB组大鼠体重、血脂[TG、胆固醇(CHOL)、低密度脂蛋白(LDL-C)]、空腹血糖(FBG)、空腹胰岛素(FINS)、骨骼肌内TG含量均明显高于NC组(P<0.05),H-Met、L-Met组血中TG、LDL的含量均较OB组下降(P<0.05);仅H-Met组观察到大鼠体重增加趋势减缓,差异有统计学意义(P<0.05);二甲双胍能明显改善肌肉组织中TG沉积(P<0.05),下调骨骼肌组织FAT/CD36的表达(P<0.05),且这些作用在H-Met组更明显(P<0.05)。结论高脂饮食可以诱导建立肥胖大鼠模型,二甲双胍可以剂量依赖性的改善肥胖大鼠血糖血脂水平,减轻骨骼肌组织的脂肪异位沉积,下调骨骼肌细胞膜的FAT/CD36的表达。Objective To observe the intervening effects of metformin on high-fat-induced obese rats with skeletal muscle fatty ectopic deposition. Methods 50 healthy male rats of four weeks age were randomly divided into normal control group（ NC group,n = 14） and high-fat group（ HF group, n = 36） ,fed with normal chow and high fat diet respectively. 12 weeks later, 32 obese rats were randomly divided into three subgroups： obesity-model group （OB group, n = 12）,low-dose metformin-treated group （L-Met group, n = 10）and high-dose metformin-treated group（ H-Met group,n = 10）. The NC group and OB group were lavaged with physiological saline, and the metformin-treated group were lavaged with the same volume but different concentrations（ 100,200 mg/kg · d） of metformin solution. At the end of the experiment, blood samples were collected to determine metabolic indexes. Adipose tissues of peri- kidney and peri-epididymis were dissected. Lipid accumulation in skeletal muscle was analyzed by the lipid-specific Oil Red O staining. Frozen sections of skeletal muscle stained with immunofluoreseence（IF） were evaluated to detect FAT/CD36 expression. Results Compared with NC group, body weight, triglyceride（TG） , total cholesterol （CHOL）, fasting blood glucose（FBG） and fasting insulin（FINS） levels of each groups in obesity model increased significantly（P 〈 0. 05）. TG, CHOL, FBG, FINS and FAT/CD36 expression levels in skeletal muscle tissue in both H-Met group and L-Met group were down-regulated with statistical difference in a dosage-dependent manner com- pared to those in OB group （P 〈 0.05 ）. Meanwhile, only high dosage of metformin could reduce body weight growth and decrease triglyeeride level in skeletal muscle tissue （P 〈 0.05 ）. Conclusion Metformin can improve hyperlipidemia, release triglyeeride eetopic deposition in skeletal muscle tissue, and down-regulate the expression of FAT/ CD36 in a dosage-dependent manner.

关 键 词：肥胖 二甲双胍 FAT CD36 胰岛素抵抗 

分 类 号：R589[医药卫生—内分泌] R345[医药卫生—内科学]