不同阶段运动干预对2型糖尿病大鼠骨骼肌leptin及其受体蛋白表达的影响

Different Exercise Stages Intervention Effects on the Expression of Skeletal Muscle in Type 2 Diabetic Rats Leptin and Its Receptor Protein

目的：1）探讨2型糖尿病糖脂代谢紊乱的机制;2）观察在2型糖尿病发生发展的不同阶段施加长期有氧运动干预改善糖脂代谢紊乱的效果及作用的机制.旨在为揭示不同运动干预在改善2型糖尿病大鼠瘦素抵抗中的作用及其作用机制提供实验依据.方法：将55只刚断乳雄性大鼠随机分为两组组,正常对照组（CON,11只）,高脂高糖组（HLG,44只）,其中正常饮食对照组用普通饲料,HLG组给与高脂高糖饮食喂养六周后.体重超过正常组25％,为肥胖模成功,再给与腹腔注射小剂量（35 mg/kg）的链脲佐菌素（STZ）,造2型糖尿病模型,将造模成功鼠按血糖水平随机分成糖尿病对照组（DC,8只）,糖尿病运动1组（DE1,8只）,糖尿病运动2组（DE2,8只）和糖尿病运动3组（DE3,8只）,分别在1～6周,7～12周和1～12周进行游泳训练,实验结束后测定血糖、胰岛素、瘦素、骨骼肌中TG、FFA含量和瘦素及其素受体的蛋白表达等指标.结果：DC组体重、腹腔脂肪、血清胰岛素、葡萄糖、瘦素和胰岛素的耐受性均显著高于CON组;而DE1-3组体重、腹腔脂肪、血清胰岛素、葡萄糖和瘦素均均出现不同程度的下降,以DE3组下降效果明显.肌肉中TG,FFA含量DC组明显高于CON组;DE1-3与DV组相比均有均下降趋势,只有DE3组有统计学差异;且DE3组的TG含量也显著低于DE2组.DC组骨骼肌中瘦素含量显著升高（P＜0.01）,但瘦素受体含量明显降低（P＜0.05）;DE1-3组与DC组相比,瘦素水平有下降的趋势,相反他们的瘦素受体含量都有升高的趋势,其中DE3组的变化有统计学意义.结论：1）高脂膳食结合小剂量的STZ诱导的2型糖尿病大鼠骨骼肌瘦素抵抗,降低了其对骨骼肌脂代谢的调节作用,导致骨骼肌脂质的过度沉积,引发了整体水平瘦素抵抗和胰岛素抵抗.2）在糖尿病发生、发展的不同阶段施加有氧训练可不同程度改善骨骼肌瘦素抵抗,改善了机体的糖脂代谢,缓解了胰岛素抵抗和瘦素抵抗,在糖尿病发生发展的全过程施加运动干预的效果更好.

Objective：1. Explore the mechanisms of glucose and lipid disorders in type 2 diabetes;2. Observed at different stages of development of type 2 diabetes exerts a long-term mechanism of aerobic exercise intervention effect and improve glucose and lipid metabolism disorders. In order to reveal the different exercise intervention in improving the effect of leptin resistance in type 2 diabetic rats and its mechanism of action to provide the experimental basis. Methods ：55 weanling male rats were randomly divided into two groups, the normal control group （ CON, 11 ）, high fat and high glucose group （ HLG, 44 ）. Among them, normal diet control group with normal feed, LG group given feeding high fat and high sugar diet for six weeks. More than normal weight group 25%, obesity model success, then give the intraperitoneal injection of small dose （35mg / kg） of streptozotocin （STZ）, Build a model of type 2 diabetes, the successful model rats were randomly divided into two groups according to blood glucose level of the diabetic control group （ DC, 8 ）, diabetic exercise group 1 （ DE1, 8 ）, diabetic＇ exercise group 2 （ DE2,8 ） and exercise diabetic group 3 （ DE3,8 ）, in 1 - 6 weeks, 7- 12 weeks and 1 - 12 weeks swimming training, at the end of the experiment, blood glucose,insulin, leptin, skeletal muscle TG, FFA content and leptin and its receptor protein expression index. Results： Tolerance to DC group, abdominal fat weight, serum insulin, glucose,leptin and insulin were significantly higher than those in group CON;In DE1 -3 group, abdominal fat weight, serum insulin, glucose and leptin were decreased in different degree, In the DE3 group decreased obviously. Muscle TG, FFA content in DC group was significantly higher than that in group CON;DE1 -3 had a decreased trend compared with the DV group, there is significant difference only in DE3 group ; And the content of TG in group DE3 were significantly lower than that of group DE2. Leptin levels in skeletal muscle of DC group increased significantly （P 〈 0. 01 ） ,but the content of leptin receptor significantly decreased （P 〈 0. 05 ） ;Compared with DE1 -3 group and DC group, Leptin levels tended to decrease, Instead of leptin receptor content they were increased, changes in the DE3 group was statistically significant. Conclusions ： 1. High - fat diet with skeletal muscle in type 2 diabetic rat leptin resistance induced by low dose STZ,To reduce the effect on the regulation of skeletal muscle lipid metabolism, lead to excessive deposition of skeletal muscle lipid, raised the overall level of leptin resistance and insulin resistance. 2. Different stages in the development of diabetes, applying the aerobic training can be improved at different extent of leptin resistance in skeletal muscle, improved glucose and lipid metabolism in the body, relieve insulin resistance and leptin resistance,in the whole process of the development of better diabetes applied exercise intervention.