【作者】 尚延侠；

【导师】 陈文鹤；

【作者基本信息】 上海体育学院 ， 运动人体科学， 2011， 博士

【摘要】 研究目的:中国的儿童少年肥胖发生率正逐年上升,肥胖严重危害其身心健康。肥胖者往往伴随着胰岛素抵抗、脂质代谢异常、慢性炎症及血管内皮功能障碍,血管内皮功能障碍的发生可能与上述因素有关。因此,本研究观察运动减肥前后肥胖儿童少年的脂质代谢、胰岛素抵抗、炎症水平及血管内皮功能的变化,探讨血管内皮功能与脂质代谢及系统炎症之间的相关性。旨在进一步探讨A-SAA等炎症因子在血管内皮功能损伤过程中的作用及运动减肥影响血管内皮功能的可能机制。研究方法:选取全封闭式运动减肥夏令营肥胖儿童少年37人。运动减肥前首先进行跑台递增负荷试验来确定运动减肥的合适强度,确定每位受试者合适的运动心率范围并制定个体化的运动处方。本研究结合健康知识教育、合理膳食、有氧运动及行为干预的综合干预手段进行减肥干预。测量运动减肥前后肥胖受试者的身体形态学指标(主要包括:身高、体重、腰围、臀围、胸围、皮褶厚度)、身体机能指标(包括血压、心率、肺活量)。测定运动减肥前后的血脂(HDL-C、LDL-C、TC、TG、ApoA、ApoB)、空腹血糖(GLU)、空腹血清胰岛素(FINS)、糖化血红蛋白(HbAlc)、血浆内皮素-1(ET-1)、血清一氧化氮(NO)、血清血管性假血友病因子(vWF)、血清可溶性细胞间黏附分子-1(SICAM-1)、血清纤溶蛋白激活物-1(PAI-1)、脂肪细胞因子(血清Adi、血清LEP、血清TNF-α、血清IL-6、血清A-SAA)的水平。分析炎症因子、血管内皮细胞因子与其他指标之间的相关性,运动减肥干预后上述指标的变化情况。研究结果:(1)运动减肥后,肥胖儿童少年的体重平均下降6.57Kg,下降了8.7%(P<0.01);BMI在运动减肥后由29.09Kg/m2下降至26.43Kg/m2,下降了9.1%(P<0.01);上臂和肩胛下角皮褶厚度之和下降12.47mm,下降了22%,有非常显著性统计学意义;体脂百分比下降了16.5%(P<0.01);腰围下降12.8cm,下降了14%(P<0.01);臀围下降9.36cm,下降了9.38%(P<0.01);腰臀比从0.91下降至0.87,下降了4.4%(P<0.01)。运动减肥后,颈围、上臂紧张围、上臂放松围皆显著下降。(2)运动减肥后,肥胖受试者的收缩压、舒张压均有非常显著性下降,血管弹性指数升高并有显著统计学意义,脉压下降但并无显著统计学意义,安静心率下降并有非常显著性统计学意义,肺活量增加并有显著统计学意义。(3)运动减肥后,受试者的空腹血糖及空腹胰岛素水平显著性下降,胰岛素抵抗指数明显下降;糖化血红蛋白水平也下降,但是并无显著性统计学意义;总胆固醇、甘油三酯、低密度脂蛋白胆固醇、载脂蛋白B水平显著性下降;载脂蛋白A及高密度脂蛋白胆固醇显著性下降,但是高密度脂蛋白胆固醇与低密度脂蛋白胆固醇的比值发生非常显著性升高(P<0.01);运动减肥后,动脉粥样硬化指数显著下降(P<0.01)。37例受试者中,总胆固醇和甘油三酯同时超过正常范围的有9例,单纯甘油三酯超过正常范围的有5例,单纯总胆固醇升高的有5例。运动干预后脂质代谢紊乱得到纠正。(4)运动减肥前男、女肥胖儿童少年LEP、Adi、A-SAA、TNF-α、LNSTNFR2、IL-6、WBC均无显著性差异。运动减肥后,男、女肥胖儿童少年的LEP、WBC水平均发生非常显著性下降(P<0.01),男、女肥胖儿童少年的Adi水平均升高并有非常显著性统计学意义,男性肥胖儿童少年的A-SAA及IL-6发生显著性下降(P<0.05),女性肥胖儿童少年的A-SAA及IL-6均发生非常显著性下降(P<0.01)。运动减肥前轻中度肥胖组与重度肥胖组相比,重度肥胖组的脂联素水平比轻中度肥胖组低27.13%(P<0.05);重度肥胖组的WBC及A-SAA水平比轻中度肥胖组分别高14.66%和23.87%(P<0.05)。运动减肥后,轻中度肥胖组LEP、IL-6水平有非常显著性下降(P<0.01),WBC下降28.85%(P<0.01),Adi水平升高16.28%(P<0.01),A-SAA下降了21.89%(P<0.05);重度肥胖组减肥后LEP、A-SAA、WBC均发生非常显著性下降,其中A-SAA下降了28.20%(P<0.01),Adi升高36.17%(P<0.01)。说明运动减肥后,体内炎症水平下降。血清Adi与腰围、BMI、AI、FINS、HOMA-IR呈负相关,与ISI、HDL、ApoA呈正相关。说明Adi与中心型肥胖有关,且随着肥胖程度的加重Adi水平下降,Adi水平下降会导致动脉硬化指数及胰岛素抵抗程度的加重,从而增加动脉粥样硬化发生的风险。LEP水平与脂肪量呈正相关,说明脂肪含量越高,瘦素水平越高,这是体内一种反馈调节的表现。(5)运动减肥后,轻中度及重度肥胖组受试者的血清NO的水平均升高(P<0.01),分别比运动减肥前升高70.75%和101.1%;血浆ET-1水平下降,亦有显著性统计学意义。说明运动减肥后血管内皮的舒缩功能得到改善。减肥前,轻中度与重度肥胖受试者的血浆vWF、血清SICAM-1、血清PAI-1、血小板计数均无显著性差异。运动减肥后,不同肥胖程度的两组受试者的血浆vWF分别下降55.88%(P<0.01)和48.94%(P<0.01);血清SICAM-1分别下降17.51%(P<0.01)和17.15%(P<0.01);血清PAI-1分别下降21.81%(P<0.05)和26.69%(P<0.01);红细胞压积分别下降5.78%(P<0.01)和4.96%(P<0.01);血小板计数分别下降22.84%(P<0.05)和24.95%(P<0.01)。以上数据说明,减肥后肥胖少年儿童的内皮凝血、黏附、纤溶功能发生显著性改善。相关性分析表明,ET-1与炎症因子TNF-α、IL-6呈显著正相关。血清NO的含量与舒张压、皮褶厚度呈显著负相关。血浆vWF与甘油三酯、血糖的对数呈正相关;SICAM-1与LEP呈正相关;PAI-1与WBC、TNF-α、IL-6、ET-1呈显著正相关。研究结论:(1)全封闭式运动减肥显著改善了肥胖受试者的身体形态、糖脂代谢紊乱及胰岛素的敏感性。(2)全封闭式运动减肥可以显著提高脂联素水平,降低瘦素的水平,有效降低肥胖受试者体内的炎症状态。提示有氧运动可能通过降低炎症标志物的水平及升高脂联素水平发挥抗炎作用,从而防止动脉粥样硬化等疾病的发生和发展。(3)血管内皮功能障碍与炎症状态有关,全封闭式运动减肥有效改善了肥胖受试者血管内皮舒缩、凝血、粘附及纤溶功能。提示运动减肥是下调炎症因子和缓解内皮功能障碍的有效手段,对于预防AS、MS等疾病的发生具有重要意义。更多还原

【Abstract】 Objective: Data shows that obesity incidence is rising year by year in China, which seriously damaged their physical and mental health. As we all know, obesity often accompanies with insulin resistance, lipid metabolic abnormalities, chronic inflammation and endothelial dysfunction, and endothelial dysfunction has some relations with the diseases above. Therefore, this study observed obese children and adolescents’blood lipid metabolism, inflammatory factors, vascular endothelial function before and after 4 weeks’aerobic exercise, explored the correlation between endothelial function and other indicators, discussed the changes of proinflammatory A-SAA after weight loss and the relationship between proinflammatory such as A-SAA and endothelial function, in order to further explore the role of proinflammatory factor A-SAA in endothelial function damage and the possible mechanisms of weight loss to endothelial function.Methods: 37 obese children and adolescents were selected from the fully closed weight camp as subjects. Before starting the exercise programme, subjects underwent a graded treadmill stress test to determine the appropriate individual level of exercise intensity. On the basis of the results, the subjects were provided with an appropriate training heart rate and given an individualized weight loss programme. The subjects were intervened with methods of health knowledge education, reasonable diet, aerobic exercise and behavior intervention. Before and after 4 weeks intervention, body morphology index (mainly includes: height, weight, waist circumference, hip circumference, chest circumference and skin-fold), body function index (including the blood pressure and heart rate, vital capacity) were measured. The blood lipid (HDL-C、LDL-C、TC、TG、ApoA、ApoB), fasting blood-glucose(FBG), fasting insulin(FINS), glycated hemoglobin, plasma endothelin-1, serum nitric oxide, serum vWF, serum soluble intercellular adhesion molecule-1, serum PAI-1, Adipocytokines(serum adiponectin, blood leptin, serum tumor necrosis factor alpha, serum IL-6, A-SAA) were also measured before and after the weight loss programme.The changes of vascular endothelial vasomotion, clotting, adhesion, fibrinolytic functions were analyzed after 4 weeks. Before and after weight loss, proinflammatory factors were analyzed, and the correlations between A-SAA and blood sugar, blood lipid and inflammatory factors were discussed. The results: (1) After weight loss intervention, the subjects’body weight dropped 6.57 kilogrammes, dropped 8.7% (P < 0.01); BMI dropped from 29.09 Kg/m2 to 26.43Kg/m~2, dropped 9.1%(P<0.01); the sum of upper arm and shoulder Angle skin-fold dropped 12.47 mm, dropped 22%(P<0.01); Body fat percentage dropped 16.5% (P < 0.01), Waist circumference declined 12.8 cm, declined 14% (P < 0.01), Hip circumference declined 9.36 cm, dropped 9.38% (P < 0.01), Waist-hip ratio dropped from 0.91 to 0.87, dropped 4.4% (P < 0.01). After the weight loss programme, neck circumference, upper arm tension circumference, upper arm relax circumference all dropped significantly.(2) After weight loss programme, obese subjects’systolic blood pressure and diastolic blood pressure declined very significally, vessel elasticity index rised and had statistical significance, pulse pressure dropped but had no statistical significance, resting heart rate dropped and had very significant statistical significance, vital capacity increased and had significant statistical significance.(3) After weight loss programme, subjects’fasting glucose and fasting insulin levels decreased significantly, insulin resistance index declined obviously, glycated hemoglobin levels also declined, but there were no significant statistical significance, total cholesterol, triglyceride and low density lipoprotein cholesterol, apolipoprotein B decreased significantly; Apolipoprotein A and high-density lipoprotein cholesterol decreased significantly, but HDL and LDL ratio increased very significantly (P < 0.01), Atherosclerosis index dropped significantly (P < 0.01). Among 37 subjects, there were 9 subjects whose total cholesterol and triglyceride beyond the normal range, 5 subjects whose triglyceride and 5 subjects whose cholesterol beyond the normal range. After weight loss programme, blood lipid returned to the normal range.(4) Before weight loss programme, there were no significant differences in the levels of leptin, adiponectin, A-SAA, tumor necrosis factor alpha, LNSTNFR2, IL-6, WBC between female and male subjects. After weight intervention, the level of leptin and WBC declined very significantly, adiponectin increased very significantly in male and female subjects (P<0.01). Serum A-SAA and IL-6 reduced significantly in male subjects (P<0.05), while very significantly in female subjects (P<0.01). Before weight loss,mild-to-moderate obesity group and group compared , adiponectin of severe obese group was lower 27.13% (P<0.05) than that of mild-to-moderate obesity group, WBC and A-SAA levels were higher 14.66% and 23.87% respectively(P<0.05). After weight loss intervention, leptin, IL-6 levels declined very significantly (P<0.01), leukocyte declined 28.85% (P<0.01), adiponectin levels increased 16.28% (P<0.01), A-SAA dropped 21.89% (P<0.05) in mild-to-moderate obesity group; leptin, A-SAA, WBC declined very significantly, A-SAA dropped 28.20% (P<0.01), adiponectin increased 36.17% in severely obese group (P<0.01). It showed that inflammation level decreased after weight loss. Serum adiponectin was correlated with waist circumference, body mass index (BMI), AI, INS, HOMA-IR negatively, correlated with ISI, HDL, ApoA positively, which shows that adiponectin had some relations with abdominal obesity and reduced with obesity. The drop of adiponectin levels would cause atherosclerosis index increasing and insulin resistance level aggravating, which would increase the risk of atherosclerosis. We also found that Leptin level was positively correlated with the fat mass. It told us that more fat mass, higher leptin, which might be the body feedback adjustment performance.(5) After 4 weeks’ weight loss programme, in mild-to-moderate and severely obese group, serum levels of nitric oxide increased significantly (P<0.01), elevated 70.75% and 101.1% respectively compared with the level before weight loss; Plasma endothelin levels droped significantly, which showed that after weight loss the vasomotion vascular endothelial function improved. Before weight loss, plasma vWF, serum SICAM-1, serum PAI-1, platelet count of mild-to-moderate and severe obese participants exited no significant differences. Severe obese participants’ HCT were higher 5.22% than that of mild-to-moderate obesity group (P<0.05). After weight loss, plasma vWF dropped 55.85% (P<0.01) and 48.94% (P<0.01)respectively, Serum SICAM-1 dropped 17.51%(P<0.01) and 17.15% (P<0.01) respectively, Serum PAI-1 dropped 21.81% (P<0.01) and 26.69% (P<0.01) respectively, HCT dropped 5.78%(P<0.01) and 4.96%(P<0.01) respectively, Platelet count dropped 22.84% (P<0.05) and 24.95% (P<0.01) respectively in the two groups. Datas above showed that after weight loss, endothelial clotting, adhesion, fibrinolytic function significantly improved. Correlation analysis showed that, ET-1 positively correlated with TNF alpha, IL-6. Serum levels of nitric oxide correlated negatively with diastolic blood pressure, skin-fold. Plasma vWF positively correlated with triglyceride, lNGLU; SICAM-1 correlated positively with LEP, PAI-1 correlated with WBC and TNF alpha, IL-6, ET-1 significantly.Conclusion: (1) Aerobic exercise significantly improved obese subjects’body shape, glucolipid metabolism disorders and insulin sensitivity. (2) Aerobic exercise significantly enhanced the level of adiponectin, reduced the level of serum leptin and inflammatory factors of the obesity in fully closed weight camp.It told us that aerobic exercise played an important role in reducing inflammatory factors’level, preventing occurrence and development of atherosclerosis. (3) Vascular endothelial dysfunction has close relationship with inflammation. Aerobic exercise improved obese subjects’vascular endothelial vasomotion, clotting, adhesion and fibrinolytic function, which showed that aerobic exercise was an effective means in reducing inflammation level and recovering endothelial dysfunction to prevent from diseases such atherosclerosis and metabolic syndrome.更多还原