有氧运动对KK-Ay小鼠骨骼肌p38 MAPK、血清TNF-α及FFA的影响

Effects of Aerobic Exercise on p38MAPK in Skeletal Muscle & Serum Levels of TNF-α and FFA of KK-Ay Mice

目的:从p38 MAPK信号转导通路的角度探讨运动降低糖尿病血糖水平的机制,为运动治疗糖尿病提供科学依据和参考。研究方法:雄性6月龄KK-Ay和C57BL/6J小鼠各12只,按血糖配对后随机分为糖尿病运动组(KE组)和糖尿病对照组(KC组);正常运动组(CE组)和正常对照组(CC组)。进行坡度0°,速度12 m/min,时间30 min的跑台运动后,实验检测p38蛋白表达和磷酸化,测定血糖浓度、血清胰岛素和TNF-α、FFA。研究结果:KK-Ay小鼠血糖高于C57BL/6J小鼠,KE组和CE组血糖分别较实验前下降了34%和25%;运动后CE组血清胰岛素浓度比CC组低55%,KE组则较KC组低43%;骨骼肌p38磷酸化水平KC组高于CC组,CE组高于C组,KE组高于KC组;血清TNF-α及FFA浓度KC组明显高于CC组,KE组明显低于KC组。结论:一次性有氧运动可以有效降低KK-Ay小鼠的血糖及血清胰岛素水平,直接激活KK-Ay小鼠骨骼肌p38磷酸化,降低血清TNF-α和FFA水平,并通过p38间接作用于TNF-α、FFA,最终达到降低血糖的效果,这可能是运动降血糖的部分分子机制。

Purpose：This study is to discuss possible mechanism of glucose-lowering through exercise from p38MAPK pathways and then provides the scientific basis and the reference for curing diabetes by exercise.Mouses：12 six-month-old male KK-Ay mouses and 12 C57BL/6J mouses were divided into four groups randomly according to the blood sugar： diabetes exercise group（KE group） and diabetes control group（KC group）;normal exercise group（CE group） and normal control group （CC group）.The experiment was carried out on a flat surface with zero degree of slope with the speed of 12 m/min;After 30-minute running,blood sugar levels,p38 protein expression and phosphorylation,blood serum FFA,insulin and TNF-α after exercise were tested.Results： Blood sugar of KK-Ay mouse was higher than the C57BL/6J＇s.Blood sugar was reduced by 34% in KE group,and 25% in CE group after a bout of acute exercise.Blood serum insulin levels in KC group were 59-fold of CC group.It was 55% lower in CE group than in CC group.It was 43% lower in KE group than in KC group.p38 phosphorylation of KC group was increased more significantly than CE group＇s in skeletal muscle.And the increase is more significant in CE group than in CC group and the same is true in KE group than in KC group.Serum TNF-αFFA of KC group was higher than the CC group obviously.It was lower in KE than in KC group.Conclusion： p38 MAPK phosphorylation was increased in skeletal muscle of KK-Ay mice.Levels of serum TNF-α and FFA was increased at the same time.Aberrant p38 MAPK signalling might contribute to the pathogenesis of insulin resistance of Ⅱ diabetes.p38 and TNF-αFFA effect on each other.All of these play the extremely vital role in insulin resistance and Ⅱ diabetes developing process together.Firstly,a bout of aerobic exercise had effect on p38 in skeletal muscle and serum TNF-αFFA of KK-Ay mouse directly.It activated of p38 phosphorylation in skeletal muscle,reduced levels of serum TNF-α and FFA,indirectly influenced TNF-α and FFA through the p38 and finally reduced the blood sugar levels.This is the partial mechanism of glucose-lowering process through exercise.