有氧运动对胰岛素抵抗小鼠骨骼肌基因表达谱的影响

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目的:研究6周有氧跑台运动对胰岛素抵抗(insulin resistance,IR)小鼠骨骼肌基因表达谱的影响。通过与安静对照组骨骼肌基因表达谱相比较,分析并筛选差异表达基因,为研究有氧运动防治IR的基因调控机制提供理论依据。方法:选用C57BL/6雄性小鼠80只,将其分为正常饮食组(NC,n=20)和IR模型组(n=60)。正常饮食组饲以基础饲料,模型组小鼠喂饲高脂饮食10周以建立IR模型。10周后,鉴定模型成立。将40只成模的IR小鼠随机分为安静对照组(HC,n=20)和运动组(HE,n=20)。HE组进行6周、5天/周、1次/天、60分钟/次、强度为75%VO2max的跑台训练。6周训练结束后24小时,分别检测小鼠口服葡萄糖耐量(OGTT),空腹血清胰岛素(FIN)水平,血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)和游离脂肪酸(FFA);提取小鼠股四头肌总RNA,经过荧光标记后进行基因芯片杂交,利用芯片扫描仪记录荧光信号,并通过相关软件对所得数据进行统计分析。结果:6周有氧运动后,运动组OGTT曲线峰值出现时间点较安静组明显前移,且峰值下降,平台期消失;运动后HE组TC、TG、FFA与HC组相比分别降低24.30%、40.56%和35.36%,HDL上升30.47%。比较HC组与HE组基因表达谱,共筛选出264个差异表达基因,其中运动后表达上调基因215个,下调基因49个,这些基因编码的蛋白涉及多个细胞信号通路。其中MAPK信号通路中有6个基因表达有差异,表达上调的基因有MAPK1、HSPB1、GNG12、ECSIT和STK3;下调的基因为TRP53。结论:6周有氧运动能够明显改善IR小鼠糖脂代谢障碍。MAPK信号通路可能参与骨骼肌细胞对运动的适应性改变,以及骨骼肌细胞对胰岛素敏感性的增强,由此推测该信号通路可能与改善机体IR密切相关。 Objective: To study the effect of aerobic treadmill exercise on the gene expression profile of skeletal muscle in insulin resistance (IR) mice at 6 weeks. By comparing with the gene expression profile of skeletal muscle in quiet control group, the differentially expressed genes were analyzed and screened, which provided a theoretical basis for studying the gene regulation mechanism of IR for aerobic exercise. Methods: Eighty male C57BL / 6 mice were divided into normal diet group (NC, n = 20) and IR model group (n = 60). The normal diet group fed with basal diet, model group mice fed a high-fat diet for 10 weeks to establish the IR model. After 10 weeks, the identification model was established. Forty IR-infused mice were randomized to a control group (HC, n = 20) and a motor group (HE, n = 20). The HE group was subjected to treadmill training at 6 weeks, 5 days / week, 1 time / day, 60 minutes / time, and intensity of 75% VO2max. The levels of oral glucose tolerance (OGTT), fasting serum insulin (FIN), total cholesterol (TC), triglyceride (TG), high density lipoprotein Total RNA was extracted from quadriceps femoris muscle, and then fluorescently labeled for gene chip hybridization. Fluorescent signals were recorded with a chip scanner and the data were statistically analyzed by related software. Results: After 6 weeks of aerobic exercise, the peak of OGTT curve of exercise group obviously progressed compared with the quiet group, and the peak value decreased and the plateau disappeared. The TC, TG, FFA of exercise group decreased by 24.30% , 40.56% and 35.36%, HDL increased by 30.47%. A total of 264 differentially expressed genes were screened from HC and HE group, including 215 up-regulated genes and 49 down-regulated genes. The proteins encoded by these genes involved in multiple cell signaling pathways. Among them, 6 genes were differentially expressed in MAPK signaling pathway, MAPK1, HSPB1, GNG12, ECSIT and STK3 were up-regulated while TRP53 was down-regulated. Conclusion: Aerobic exercise for 6 weeks can significantly improve glucose and lipid metabolism in IR mice. MAPK signaling pathway may be involved in the adaptive changes of skeletal muscle cells to exercise, and insulin sensitivity of skeletal muscle cells increased, suggesting that the signal pathway may be closely related to the improvement of body IR.
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