研究目的：本研究通过高脂饮食诱导的肥胖大鼠模型，观察跑台运动对大鼠肥胖相关指标和骨骼肌形态的变化，以及骨骼肌和脂肪组织中白介素(interleukin，IL)-15及其受体的mRNA和蛋白表达的变化，探讨骨骼肌IL-15在运动调节体成分中的作用机制，为运动防治肥胖提供新的靶点。研究方法：5周龄雄性SD大鼠随机分为基础对照组（control, Con, n=8）和高脂实验组（high-fat diet, HFD, n=32），分别进行普通饲料和高脂饲料喂养，12周后根据体重大小筛选出16只肥胖大鼠，高脂肥胖大鼠随机分为高脂安静组（HFD, n=8）和高脂运动组（HFD+treadmill, n=8），运动组大鼠进行26m/min 跑台运动，每次运动1小时，每周运动5次，共8周。末次运动结束后，禁食过夜，20%乌拉坦麻醉，取材后分别进行如下测定：放免法测定大鼠血浆和比目鱼肌(soleus, SOL) 、腓肠肌(gastrocnemius, GAS)IL-15含量；Real-time PCR测定比目鱼肌、腓肠肌和睾周脂肪IL-15及其受体的mRNA表达水平；Western Blot的方法检测腓肠肌、睾周脂肪IL-15Rα，腓肠肌肌球蛋白重链(myosin heavy chain, MHC)以及睾周脂肪磷酸化和总细胞外信号调节激酶(phosphorylated extracellular signal-regulated kinase, p-ERK；total extracellular signal-regulated kinase, t-ERK)的蛋白表达变化；全自动生化分析仪测定血脂水平；HE染色观察腓肠肌的肌纤维横截面积(cross sectional area，CSA)。研究结果：1. 与对照组相比，HFD组大鼠体重和lee指数均显著升高（p<0.01）；脂肪组织体积显著增加（p<0.01），血脂紊乱。8周的跑台运动显著降低了HFD大鼠体重和lee指数（p<0.01）；显著减少了脂肪组织体积（p<0.01），改善了肥胖大鼠血脂异常。与对照组相比，HFD组大鼠血浆和腓肠肌IL-15含量显著降低，腓肠肌IL-15 mRNA表达显著下降（p<0.05），而比目鱼肌没有变化；肥胖大鼠睾周脂肪IL-15Rα的mRNA和蛋白表达显著性降低（p<0.01）。8周的跑台运动显著升高了大鼠血浆、比目鱼肌和腓肠肌IL-15的含量，以及比目鱼肌和腓肠肌IL-15的mRNA表达。同时，显著升高了睾周脂肪IL-15Rα的mRNA及其蛋白表达（p<0.05）。结果表明，跑台运动逆转了肥胖大鼠血浆、骨骼肌IL-15和脂肪组织IL-15Rα的表达下调。与对照组相比，IL-15处理的肥胖大鼠睾周脂肪p-ERK的蛋白表达显著性下降(P<0.01)；8周的跑台运动显著性升高IL-15处理的肥胖大鼠睾周脂肪中p-ERK的蛋白表达(P<0.01)。结果表明，跑台运动能够逆转IL-15诱导的肥胖大鼠脂肪组织p-ERK的蛋白表达下降，脂肪组织IL-15R反应性提高。2. 与对照组相比，HFD组大鼠腓肠肌/胫骨长显著降低（p<0.05），腓肠肌肌纤维CSA显著减小(P<0.01)，而比目鱼肌没有显著变化。8周的跑台运动显著增加了大鼠比目鱼肌/胫骨长和腓肠肌/胫骨长（p<0.01）；腓肠肌肌纤维CSA显著增粗（p<0.01）。结果表明肥胖大鼠出现了显著的骨骼肌萎缩，而跑台运动显著改善肥胖大鼠骨骼肌萎缩。与对照组相比，HFD组大鼠腓肠肌MHC的蛋白表达，IL-15含量和mRNA表达显著降低（p<0.05）；同时，腓肠肌IL-15Rα的mRNA表达和蛋白表达显著性降低（p<0.05）。8周的跑台运动显著升高HFD大鼠腓肠肌MHC的蛋白表达（p<0.05），IL-15的含量和mRNA表达（p<0.01）；同时，显著升高了腓肠肌IL-15Rα的mRNA和蛋白表达（p<0.05）。结果表明跑台运动逆转了肥胖大鼠骨骼肌MHC、IL-15及其受体IL-15Rα的表达下调。与单纯的对照组和高脂肥胖组相比，IL-15孵育均显著升高大鼠离体腓肠肌MHC的蛋白表达（p<0.05）。结果表明，IL-15促进大鼠骨骼肌MHC的表达。研究结论： 1. 跑台运动减轻大鼠肥胖，促进肥胖大鼠骨骼肌IL-15及脂肪组织IL-15Rα的表达，提高IL-15R反应性； 2. 跑台运动改善肥胖大鼠骨骼肌萎缩，促进肥胖大鼠骨骼肌IL-15/IL-15Rα表达；IL-15促进骨骼肌MHC的表达。提示运动可能通过上调肥胖时降低的骨骼肌IL-15/IL-15Rα和脂肪组织IL-15Rα的表达，减轻体脂，增加瘦体重，改善身体体成分。因此，骨骼肌IL-15可能是运动调节体成分的机制之一。

Objective: Used the model of high-fat diet induced obese rat, This research observed that the changes of treadmill running on obesity related markers and the morphology of skeletal muscle, tested that the expression of mRNA and protein of IL-15/IL-15Rα in skeletal muscle and IL-15Rα in adipose tissue, investigated that the effects and mechanism of IL-15 in skeletal muscle during treadmill running regulating body composition, provided a new target for exercise on the therapy of obesity.Methods: 5 weeks age male SD rats were randomly divided into control group (n=16) and high-fat diet group (n=34), and were respectively fed for general diet and high-fat diet. After 12 weeks of a high fat diet, only 16 obese rats were elected by the weight size, and high-fat diet obese rats were randomly divided into only high-fat diet group (HFD, n=8) and high-fat diet + treadmill running group (HFD + treadmill, n=8), obese rats underwent treadmill running at 26 m/min (60 min each, 5 days/week for 8 weeks). At the end of the dietary and exercise protocol, rats fasted overnight but had free access to water and were anesthetized with use of 20%urethane. The rats were drawn materials and were respectively made the determination as follows: Radioimmunoassay (RIA) method for determination of IL-15 content in the plasma, soleus and gastrocnemius; Real-time PCR for determination of IL-15 and its receptor mRNA expression levels in the soleus, gastrocnemius and epididymal fat; Western Blot for detection of IL-15Rα protein expression in the gastrocnemius, epididymal fat, MHC protein expression in the gastrocnemius and p-ERK/t-ERK protein expression of the epididymal fat; Automatic biochemical Analyzer for determination of the plasma lipid profile; HE staining for determination of gastrocnemius muscle cross sectional area.Results: 1. Compared with control, the body weight and lee index of HFD rats were significantly raised (p<0.01), the accumulation of adipose tissue in HFD rats was increased (p<0.01), and the plasma lipid profile in HFD rats was disordered. Treadmill running of 8 weeks significantly reduced the body weight and lee index of HFD+treadmill rats (p<0.01), decreased the accumulation of adipose tissue in HFD+treadmill rats (p<0.01), and significantly improved the plasma lipid profile in HFD+treadmill rats. Compared with control, IL-15 content in plasma and gastrocnemius of HFD rats was significantly reduced, the expression of IL-15 mRNA in gastrocnemius of HFD rats was decreased (p<0.05), but there were no changes in soleus, the expression of IL-15Rα mRNA and protein in epididymal fat of HFD rats was significantly reduced (p<0.01). Treadmill running of 8 weeks raised IL-15 content in plasma, soleus and gastrocnemius of HFD+treadmill rats, significantly increased the expression of IL-15 mRNA in soleus and gastrocnemius of HFD+treadmill rats, raised the expression of IL-15Rα mRNA and protein in epididymal fat of HFD+treadmill rats (p<0.05). These results showed that treadmill running reversed the downregulated expression of IL-15 in plasma and skeletal muscle and IL-15Rα in adipose tissue of obese rats. Compared with control, the expression of p-ERK protein in adipose tissue explants of HFD rats incubated with IL-15 in vitro was significantly reduced (P<0.01). Treadmill running of 8 weeks significantly increased the expression of p-ERK protein in adipose tissue explants of HFD+treadmill rats incubated with IL-15 in vitro (P<0.01). The results suggested that treadmill running reversed the downregulated expression of p-ERK protein in adipose tissue explants of obese rats incubated with IL-15 in vitro, and raised the reactivity of IL-15R in adipose tissue.2. Compared with control, the ratio of gastrocnemius to tibial length in HFD rats were reduced (p<0.05), the CSA of gastrocnemius was smaller (p<0.01), but there were no significant changes in soleus. Treadmill running of 8 weeks significantly increased the ratio of gastrocnemius to tibial length, the ratio of soleus to tibial length in HFD+treadmill rats (p<0.01), the CSA of gastrocnemius was larger (p<0.01). These results showed that the obese rats had significant skeletal muscle atrophy, but treadmill running improved skeletal muscle atrophy in obese rats. Compared with control, the expression of MHC protein, IL-15 content and the expression of IL-15 mRNA in gastrocnemius of HFD rats were significantly decreased (p<0.05), the expression of IL-15Rα mRNA and protein (p<0.05) in gastrocnemius of HFD rats were significantly decreased. Treadmill running of 8 weeks significantly raised the expression of MHC protein (p<0.05), IL-15 content and the expression of IL-15 mRNA (p<0.01) in gastrocnemius of HFD+treadmill rats, increased the expression of IL-15Rα mRNA and protein (p<0.05) in gastrocnemius of HFD+treadmill rats. These results suggested that treadmill running reversed the downregulated expression of MHC/IL-15/IL-15Rα in skeletal muscle of obese rats. Compared with control and HFD, the expression of MHC protein in gastrocnemius of rats incubated with IL-15 in vitro was significantly raised (p<0.05). The results showed that IL-15 increased the expression of MHC protein in skeletal muscle of rats.Conclusion: 1. Treadmill running inhibited obesity, promoted the expression of IL-15 in skeletal muscle and IL-15Rα in adipose tissue, raised the reactivity of IL-15R in adipose tissue; 2. Treadmill running improved skeletal muscle atrophy in obese rats, promoted the expression of IL-15/IL-15Rα in skeletal muscle; IL-15 increased the expression of MHC in skeletal muscle. These suggested that exercise which might promote the expression of IL-15/IL-15Rα in skeletal muscle and the expression of IL-15Rα in adipose tissue, reduced body fat, increased lean mass, improved body composition. Therefore, IL-15 in skeletal muscle may be one of effects and mechanism during exercise regulating body composition.