运动对高脂喂养大鼠胰岛素抵抗的治疗作用

The therapeutic effect of exercise on insulin resistance induced by a high fat diet

目的观察运动对高脂饮食喂养大鼠胰岛素抵抗（IR）的影响，并初步探讨其机制。方法将30只雄性Wistar大鼠分为对照组及高脂组，分别给予基础饲料和高脂饲料喂养；高脂组大鼠经喂养18周后制成IR模型，并进一步细分为静息组和运动组，继续给予高脂饲料喂养，运动组同时进行游泳训练，共持续6周。于实验进行24周后处死各组大鼠，检测各组大鼠血液中游离脂肪酸（FFA）水平及骨骼肌中甘油三酯（TG）含量，同时应用蛋白免疫印迹法检测各组大鼠骨骼肌中一磷酸腺苷活化蛋白激酶仪（AMPKα）的磷酸化水平。结果实验进行24周后，与对照组比较，发现静息组大鼠胰岛素敏感性显著降低，FFA水平及骨骼肌中TG含量明显增高，骨骼肌中AMPKα磷酸化水平降至对照组水平的48．7％；与静息组比较，运动组大鼠胰岛素敏感性及骨骼肌中AMPKα磷酸化水平均明显提高，FFA水平及骨骼肌中TG含量则显著降低；但与对照组比较，运动组大鼠FFA水平及骨骼肌中TG含量依然偏高，胰岛素敏感性及骨骼肌中AMPKα磷酸化水平仍然偏低。结论运动干预可改善由高脂饮食诱导的IR，其治疗机制可能与降低血液中FFA水平及减轻骨骼肌中脂质异位沉积有关。

Objective To observe the effect of exercise on insulin resistance induced by a high fat diet and to explore the underlying mechanism. Methods Thirty healthy male Wistar rats were randomly divided into a normal control group （ NC group） and a high-fat group （ HF group） , fed with normal chow and a high fat diet respectively. Eighteen weeks later, insulin resistance had appeared in the HF group. The HF group was then randomly subdivided into a high-fat diet control group （HC group, fed a high fat diet） and an exercise group （HE group, fed a high fat diet and subjected to swimming training for 6 weeks）. After 24 weeks, an insulin sensitivity index was calculated. Serum free fatty acid （FFA） and skeletal muscle triglyceride （TG） were detected. Phosphorylation of adenosine monophosphate kinase-α （AMPKα） in skeletal muscle was detected by Western blotting. Results At twenty-four weeks the insulin sensitivity of the HC group had decreased significantly compared to the NC group. Serum FFA level and skeletal muscle TG content had both increased. Average phosphorylation of AMPKα in the HC group decreased to 48.7% of the NC group average. Compared to the HC group, insulin sensitivity and phosporylation of AMPK-α were elevated significantly in the HE group. Serum FFA level and skeletal muscle TG content were both lower. However, compared to the NC group, both serum FFA level and skeletal muscle TG content had increased in the HE group, while insulin sensitivity and phosphorylation of AMPKα had significantly decreased. Conclusions Exercise can significantly improve insulin resistance induced by a high-fat diet through decreasing serum FFA level and ectopic lipid accumulation in skeletal muscle.