罗格列酮对高脂喂养大鼠骨骼肌PGC-1α和GLUT4表达的影响

Effects of rosiglitazone on the expressions of PGC-1α and GLUT4 in skeletal muscles of aged rats fed by high-fat diets

目的观察罗格列酮对高脂饮食喂养老年大鼠骨骼肌过氧化物酶体增生物激活受体γ共激活因子1α(PGC-1α)、葡萄糖转运蛋白4(GLUT-4)表达的影响以及胰岛素敏感性的变化。方法 21~23月龄的老年Wistar大鼠被随机分为对照组、高脂组、高脂+罗格列酮干预组(干预组),每组20只,对照组给予基础饲料,高脂组给予高脂饲料,干预组在给予高脂饲料同时增加罗格列酮灌胃,3 mg·kg-1·d-1。检测喂养8周末3组血清三酰甘油、游离脂肪酸、骨骼肌三酰甘油水平、血糖相关指标[空腹血糖、空腹胰岛素、葡萄糖输注率]和体重。应用正常葡萄糖高胰岛素钳夹试验评估胰岛素敏感性,之后处死老鼠取材,检测其骨骼肌PGC-1α和GLUT4的mRNA及蛋白表达水平的变化。结果高脂喂养8周后,高脂组空腹血清三酰甘油、血清游离脂肪酸及骨骼肌中三酰甘油的检测结果与对照组比较明显升高,葡萄糖输注率明显下降,差异均有统计学意义(P<0.05)。与高脂组比,干预组血清三酰甘油、血清游离脂肪酸及骨骼肌三酰甘油水平较明显下降(P<0.05),葡萄糖输注率比较对照组升高(P<0.05)。与对照组比较,高脂组骨骼肌PGC-1α和GLUT4的表达下降,干预组PGC-1α和GLUT4的表达均显著高于高脂组(P<0.05),但仍低于对照组(P<0.05)。结论高脂饮食能够诱导大鼠产生胰岛素抵抗状态,伴有PGC-1α及GLUT4在骨骼肌中表达下调,罗格列酮干预后可改善胰岛素抵抗状态,增加骨骼肌PGC-1α及GLUT4的表达。

Objective To investigate the effects of rosiglitazone（ RSG） on the expressions of PGC-1α and GLUT4 in skeletal muscles of aged rats fed by high-fat diets,and to observe the changes of insulin sensitivity. Methods The male Wistar rats aged 21 ~ 23 months were divided into three group： control group（ n = 20）,high-fat diet group（ HF group,n = 20）and RSG intervention group（ high-fat diet ＋ RSG,n = 20）. At the end of the 8 th week,the insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp technique. The expression levels of PGC-1α and GLUT4 in skeletal muscle were detected by polymerase chain reaction（ PCR） and Western Blot,respectively. Results As compared with those in control group,the serum levels of triacylglycerol and free fatty acids as well as the triglyceride levels in skeletal muscles in HF group were significantly increased at the end of the 8 th,however,the glucose infusion rate in HF group was significantly decreased（ P〈0. 05）. As compared with those in HF group,the serum levels of triacylglycerol and free fatty acids as well as the triglyceride levels in skeletal muscles in RSG intervention group were significantly decreased at the end of the 8 th,however,the glucose infusion rate in HF group was significantly increased（ P〈0. 05）. Moreover,as compared with those in control group,the expression levels of PGC-1α and GLUT4 in skeletal muscles in HF group were significantly decreased,however,the expression levels of PGC-1α and GLUT4 in RSG intervention group were significantly higher than those in HF group,but,which were still significantly lower than those in control group（ P〈0. 05）. Conclusion The high-fat diet can induce insulin resistance of rats,with down-regulating of expresions of PGC-1α and GLUT4 in skeletal muscles of aged rats fed by high-fat diet. Moreover RSG intervention can improve insulin resistance and increase the expressions of PGC-1 and GLUT4 in skeletal muscle.