有氧运动对胰岛素抵抗小鼠骨骼肌基因表达谱的影响

Gene Expression Profile in Response to Aerobic Exercise in Skeletal Muscle of Mice with Insulin Resistance

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 provide theoretic evidence of preventive effect of exercise on the insulin resistance（IR）.Methods Sixty male C57BL/6 mice were randomly divided into normal chow control group and IR model group.They were fed with normal chow and high fat diet,respectively.After 10 weeks,IR model group were randomly divided into high fat diet control group（HC） and high fat diet exercise group（HE）.HE group was required to run on a treadmill for 6 weeks with the intensity of 75%VO2max.After completion of 6-week exercise,oral glucose tolerance test（OGTT）,fasting serum insulin level（FIN）,total cholesterol（TC）,triglyceride（TG0,high density lipoprotein（HDL）and free fatty acids（FFA）were detected 24 hours later.Total RNA from extracted quadriceps femoris was labeled with fluorescent dye for microarray hybridization.And their slides were scanned to generate gene lists with corresponding fluorescence intensity data.Results After 6-week exercise,comparing to HC group,the peak value of OGTT curve in HE group decreased significantly and the time point of OGTT peak shifted forward.Mean while the platform stage eliminated.TC,TG and FFA in HE group decreased by 24.30%,40.56% and 35.36%,respectively,as compared with HC group,while HDL in HE group increased by 30.47%.264 genes differentially expressed in the HE group as compared with HC group.Among the 264,215 genes were up-and 49 down-regulated.The genes encode protein involved in several signaling pathways.Four genes（MAPK1,HSPB1,ECSIT and STK3）were up regulated and one（TRP53） was down regulated in the MAPK signaling pathway.Conclusion 6-week aerobic exercise improved glucose and lipid metabolism in IR mice.6 differentially expressed genes were found to be involved in the MAPK signaling pathway,probably related to the improved adaptation of skeletal muscle cells to the exercise,and elevation of insulin sensitivity,and thus improved the IR.