目的:探讨高脂饮食、有氧运动和/或IL-6 sh RNA干扰与机体胰岛素抵抗发生的关系,并研究IL-6与AMPK在运动抑制胰岛素抵抗发生中的作用。方法:采用8周高脂饮食建立大鼠胰岛素抵抗模型,同时在此过程中采用有氧运动和/或sh RNA技术以沉默IL-6基因表达。72只健康SD雄性大鼠随机分成9组:安静普通饲料注射生理盐水组、安静普通饲料注射空白载体组、安静普通饲料注射IL-6sh RNA载体组;安静高脂饲料注射生理盐水组、安静高脂饲料注射空白载体组、安静高脂饲料注射IL-6 sh RNA载体组;运动高脂饲料注射生理盐水组、运动高脂饲料注射空白载体组、运动高脂饲料注射IL-6 sh RNA载体组。每组8只。运动组大鼠进行跑台有氧训练,每周6天,每天1次。实验鼠每2周分别尾部静脉注射生理盐水、空白载体或IL-6 sh RNA载体1次。连续干预8周后检测空腹血糖、空腹胰岛素和葡萄糖输注率以及血清IL-6浓度、骨骼肌IL-6 mRNA水平、AMPK蛋白含量和GLUT4mRNA水平。结果:与安静普通生理盐水组相比,除运动高脂组外的其它各组空腹血糖和空腹胰岛素显著增加,葡萄糖输注率显著降低(P〈0.05,P〈0.01);高脂和/或运动导致血清IL-6与骨骼肌IL-6mRNA水平、AMPK蛋白和GLUT4 mRNA水平显著上升(P〈0.05或P〈0.01);注射IL-6 sh RNA载体组与对照组相比,除安静普通载体组AMPK蛋白含量无变化,其它各对照组的血清IL-6浓度、骨骼肌IL-6 mRNA、GLUT4 mRNA水平及AMPK蛋白含量均显著下降(P〈0.05,P〈0.01)。结论:大鼠8周高脂饮食形成胰岛素抵抗。有氧运动可以抑制或减轻机体胰岛素抵抗发生,在一定程度上通过激活IL-6和AMPK起作用。IL-6可能通过激活GLUT4 mRNA降低血糖。AMPK可能是有氧运动抑制或改善胰岛素抵抗的另一重要因子。
Objective To investigate the effects of AMP-activated protein kinase(AMPK)and IL-6 on inhibition of insulin resistance(IR)during aerobic exercise. Methods 72 healthy male SD rats were randomly and equally divided into 9 groups:sedentary ordinary feed plus injection of physiological saline group,sedentary ordinary feed plus injection of blank vector group,sedentary ordinary feed plus injection of IL-6 sh RNA vector group,sedentary high fat feed plus injection of physiological saline group,sedentary high fat feed plus injection of blank vector group,sedentary high fat feed plus injection of IL-6sh RNA vector group,exercise high fat diet plus injection of physiological saline group,exercise high fat feed plus injection of blank vector group, and exercise high fat feed plus injection of IL-6 sh RNA group.The rats in all exercise groups underwent treadmill aerobic training,once a day,6 days a week for 8weeks. Injection of saline or empty vector or IL-6 sh RNA was done once every two weeks. Levels of fasting blood glucose(FG)and fasting insulin(FI),glucose infusion rate(GIR),concentration of serum IL-6,level of skeletal muscle IL-6 mRNA,AMPK protein content and level of GLUT4 mRNA were determined after 8-week continuous intervention. Results Compared with sedentary ordinary feed plus injection of physiological saline group,the FG and FI in all groups except the exercise high fat group increased and GIR decreased significantly(P 〈 0.05 or P 〈 0.01). The level of serum IL-6,skeletal muscle IL-6 mRNA,AMPK protein and GLUT4 mRNA increased significantly in high fat diet and / or exercise rats(P 〈 0.05 or P 〈 0.01). Compared with the injection of IL-6 sh RNA vector group,the level of skeletal muscle IL-6 mRNA,GLUT4 mRNA and AMPK protein in all the other groups except the AMPK protein content in sedentary ordinary feed plus injection of IL-6 sh RNA vector group decreased significantly(P 〈 0.05 or P 〈 0.01). Conclusion Aerobic exercise inhibits and / or reduces the insulin resistan