【作者】 陈刚；

【导师】 丁树哲；

【作者基本信息】 华东师范大学 ， 运动人体科学， 2010， 硕士

【摘要】 糖尿病是各种致病因子作用于机体导致胰岛功能减退、胰岛素抵抗等而引发的糖、蛋白质、脂肪、水和电解质等一系列代谢紊乱综合征,也是全世界发病率和病死率最高的5种疾病之一。胰岛素抵抗与糖尿病之间有着密切的联系,在Ⅱ型糖尿病患者当中,高达90%的患者机体内出现了IR。后天性的高脂膳食和先天性的遗传糖尿病都会引起胰岛素抵抗指数的提高。长期耐力运动能够促进线粒体生物发生,提高线粒体功能,不但能够缓解高脂膳食对机体的负作用,还能对糖尿病患者的机体起到积极的改善效果。PGC-1α是体内的一种转录共同激活因子,在肌纤维类型的转化、葡萄糖代谢、脂肪酸氧化以及线粒体生物发生等方面起着重要的调节作用；ERRa是PGC-1α的重要效应器,被PGC-1α激活后能够扩大PGC-1α的级联效应,同样在机体能量代谢和线粒体生物发生方面有着重要的作用；NRF-2受到PGC-1α、ERRa的调控,是与呼吸链表达有关的重要转录调节蛋白因子。当受到刺激时,可能通过PGC-1α-ERRa-NRF-2信号通路诱导线粒体的生物发生,从而产生适应性的改变以维持机体健康。目的：研究耐力训练在不同膳食、糖尿病病理条件下大鼠骨骼肌PGC-1α、ERR、、NRF-2基因表达的影响,探讨耐力训练对机体线粒体生物发生和呼吸链的影响、对高脂膳食机体内胰岛素抵抗以及对先天性Ⅱ型糖尿病患者病情的影响机制。方法：将40只雄性SD大鼠,4周龄,体重100±5g随机分成SD普通膳食对照组(C)、SD普通膳食耐力训练组(E)、SD高脂膳食对照组(H)、SD高脂膳食耐力训练组(HE),每组10只；同时将12只雄性GK大鼠,8周龄,体重250±5g随机分成GK对照组(G)和GK耐力运动组(GE),每组6只。SD耐力运动组大鼠和GK耐力运动组大鼠分别进行8周和6周跑台训练,每周训练6天,每天一次,起始跑速为13m/min,最大速度不超过16.7m/min,SD耐力运动组前四周每天训练40分钟,后四周每天训练1小时。GK耐力运动组第1周训练30分钟,2周后逐渐递增至1小时,并保持3周。经过饲养,末次运动结束24-48h内处死各组大鼠,测大鼠血糖和血清胰岛素水平,计算胰岛素抵抗指数反映胰岛素抵抗情况Real-time PCR测定鼠骨骼肌PGC-1、mRNA、ERRαmRNA和NRF-2 mRNA水平。结果：(1)体重：高脂膳食会显著提高SD大鼠的体重；耐力训练能够有效的控制由于高脂膳食所导致的体重增长,但对GK大鼠体重无显著性影响。(2)胰岛素抵抗指数：高脂膳食显著提高SD大鼠胰岛素抵抗指数；耐力训练能够显著降低高脂膳食SD大鼠和GK大鼠的血糖水平以及胰岛素抵抗指数；(3)高脂膳食对SD大鼠骨骼肌PGC-1α、ERRα与NRF-2 mRNA均未产生显著性影响。(4)耐力训练显著降低高脂膳食SD大鼠和GK大鼠骨骼肌内PGC-1αmRNA的表达。(5)耐力训练显著降低GK大鼠骨骼肌内ERRα和NRF-2 mRNA的表达,但未对高脂膳食SD大鼠骨骼肌内ERRα和NRF-2 mRNA产生显著影响。结论：(1)耐力训练可以显著控制高脂膳食大鼠体重增长速度；(2)无论是后天性高脂膳食,还是先天性糖尿病所导致的胰岛素抵抗水平过高的现象,都可以通过耐力运动得到缓解。(3)耐力训练会降低GK大鼠骨骼肌内PGC-1α、ERRα与NRF-2 mRNA的表达,并降低高脂膳食SD大鼠PGC-1αmRNA的表达。耐力运动对PGC-1α、ERRα和NRF-2 mRNA的影响机制,还需要进一步的研究。更多还原

【Abstract】 Diabetes is a series of metabolic disorder syndrome induced by a variety of pathogenic factors acting on the body leading to islet dysfunction and insulin resistance,and metabolic disorder of glucose、protein、fat、water and electrolytes. It’s also one of the diseases with highest morbidity and mortality. Insulin resistance and diabetes are closely linked, in type 2 diabetes patients, up to 90% of the body there were symptoms of insulin resistance. The the improvement of insulin resistance index could be caused either by the acquired a high-fat diet or the congenital genetic diabetes.The long-term endurance exercise can promote the biosynthesis of mitochondria、improve mitochondrial function,not only can alleviate the negative effects of High-fat diet on the body, but also have a positive improvement in the diabetic patients.PGC-1αis a transcriptional co-activator factor in vivo,and plays an important role in the regulation of in the transformation of muscle fiber type, glucose metabolism, fatty acid oxidation and mitochondrial biosynthesis; ERRa is an important effect device of PGC-la when activated by PGC-1α,ERRa would expand the cascade effect of PGC-1α, so it Also plays an important role in the body energy metabolism and mitochondrial bio-synthesis;NRF-2, which mediated by PGC-1αand ERRa, regulates the expression of important transcription regulatory protein factor in the respiratory chain. When are stimulated, PGC-la-ERRa-NRF-2 pathway may induce the biosynthesis of mitochondria to generate adaptive stress, in order to maintain the body’s health.Objective:The aim of this study was to investigate the effects of endurance training on the expression of PGC-la,ERRa, NRF-2 genes in the high-fat diet rats, as well as GK rats’ skeletal muscle;the effects of endurance exercise on the body’s biological synthesis, the high-fat diet bodys’insulin resistance, and the effect on congenital diabetes disease.Methods:The 40 male SD rats,about 4 weeks old,weighing 100±5g were randomly divided into SD normal diet control group (C),SD ordinary diet endurance training group(E),SD high-fat diet the control group (H) and SD high-fat diet endurance training group (HE), n=10 each group;At the same time 12 GK male rats, about 8 weeks of age, weighing 250±5g were randomly divided into GK control group (G), and GK endurance exercise group (GE),n=6 each group.SD endurance exercise rats take 8 weeks of treadmill training, while GK endurance exercise rats take 6 weeks, training six days a week, starting with a speed of of 13m/min, a maximum speed of no more than 16.7m/min.At first, SD endurance exercise rats takes four weeks training 40 minutes a day training, then takesl h/day training for four weeks.GK endurance exercise rats take a 30 minutes’training at the first week, then in the next two weeks, the training time gradually adds to 60 minutes and keeps for 3weeks.The rats were killed in the time during 24～48 hours after the last time exercise.Detected the blood glucose and plasma insulin levels in each group, the situation of insulin resistance were reflected by insulin resistance index.mRNA levels of PGC-1α,ERRa and NRF-2 of rats’skeletal muscle were determined using real-time PCR.Results:(1)Body Weight:High-fat diet can significantly improve the body weight.Endurance exercise can effectly control the weight gain caused by high-fat diet, but don’t have significantly effect on the GK rats’weight-gainning.(2)Insulin Resistance Index:Endurance exercise can significantly reduce the level of blood glucose level and insulin resistance index of high-fat diet rats and the GK rats;(3)High-fat diet has no significant effect on the expression of PGC-1α, ERRa and NRF-2 mRNA in the SD rats’muscle.(4)Endurance exercise significantly reduces the expression of PGC-1αmRNA in the high-fat diet SD rats and GK rats’skeletal muscle;(5)Endurance exercise significantly reduces the expression of ERRa and NRF-2 mRNA in the GK rats’skeletal muscle, while has no significant effect on the expression of ERRa and NRF-2 mRNA in the high-fat diet rats’skeletal muscleConclusion:(1)Endurance training can significantly control the body weight increase of the high-fat diet-rats(2)Endurance exercise can alleviate the too high-expressed-insulin resistance index, no matter it’s caused by the high-fat diet or the congenital diabetes mellitus(3)Endurance exercise can reduce the expression of PGC-1α, ERRa and NRF-2 mRNA in the GK rat skeletal muscle, and reduce the expression of PGC-1αmRNA in the high-fat diet rats.We need to do further study to know the mechanism that the affect of endurance exercise on the mRNA expression of PGC-1α, ERRa and NRF-2.更多还原