Calpain2通过ATG7在运动改善胰岛素抵抗中的作用研究

发布时间：2018-03-09 18:11

  本文选题：胰岛素抵抗　切入点：运动　出处：《上海师范大学》2017年硕士论文　论文类型：学位论文

【摘要】：胰岛素抵抗(Insulin Resistance,IR)是指由于胰岛素信号转导减弱或受阻,使得胰岛素生理作用减弱,进而导致胰岛素敏感组织(肝脏、骨骼肌、脂肪)对葡萄糖摄取和利用的效能降低。研究认为不合理的膳食结构,特别是高脂膳食,加上久坐不运动的生活方式,是引起IR的重要原因。Calpain2一般在正常生理情况下微量表达,只有在病理情况下异常升高。ATG7是自噬相关基因参与脂代谢的表达,大量研究证实,Calpain2的异常升高会引起ATG7的表达下降,干扰胰岛素信号转导通路。运动作为一种有效的非药物防治手段,研究表明,运动可有效地降低Calpain2的表达而延缓IR的发生,但其具体作用机制尚未完全阐明。因此,本文旨在以高脂饮食喂养诱导大鼠产生IR为模型,以Calpain2/ATG7为切入点,探讨Calpain2/ATG7介导运动对高脂饮食大鼠IR的影响极其相关机制。研究目的:本研究探讨运动对高脂饮食大鼠胰岛素抵抗的干预作用及Calpain2通过ATG7在运动干预胰岛素抵抗中的作用,分析运动改善胰岛素抵抗的可能机制。为预防和治疗胰岛素抵抗提供更科学的理论依据。研究方法:以30只SD大鼠为实验对象,随机分为3组:○1普通饮食对照组(C组),○2高脂饮食IR模型组(H组),○3高脂饮食IR模型运动组(HE组)。通过8周高脂饲料(热卡比为蛋白质22%,脂肪45%,碳水化合物33%,提供能量约为5305Kcal/1000g)喂养建立大鼠IR模型,同时对大鼠实施无负重游泳运动干预。综合利用体重、空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI)评价动物模型的建立和运动干预的效果;通过观察运动对高脂饮食诱导的IR大鼠肝脏ATG7、Calpain2、IRS-1、p-IRS-1(ser307)、AKT、p-AKT(ser473)蛋白的表达,分析运动对高脂饮食诱导IR大鼠肝脏组织Calpain2/ATG7和IR经典信号通路相关因子的表达。探讨Calpain2/ATG7在胰岛素抵抗过程中的作用以及运动在其中的作用。研究结果:1、8周高脂喂养建立大鼠IR动物模型的评价:与C组大鼠相比,H组大鼠的FINS和HOMA-IR均显著升高(p0.01,p0.01),ISI显著降低(p0.01)。大鼠FBG无显著性差异(p0.05)。与H组大鼠相比,HE组大鼠的FINS和HOMA-IR均显著降低(p0.05,p0.01),ISI显著增加(p0.01)。大鼠FBG无显著性差异(p0.05)。2、各组大鼠体重的变化:实验前各组大鼠体重无显著性差异(p0.05)。实验期间大鼠饲养条件良好毛色光亮,生长发育正常。8周实验后,H组大鼠体重显著高于C组(p0.01),HE组大鼠体重显著低于H组大鼠(p0.01),HE组大鼠体重与C组大鼠体重无显著差异(p0.05)。3、8周规律游泳运动后各组大鼠血脂的变化:与C组大鼠相比,H组大鼠的TG、TC、LDL-C均显著升高(p0.05,p0.05,p0.01),HDL-C显著降低(p0.05)。与H组大鼠的血脂相比,HE组大鼠的TG、TC、LDL-C均显著降低(p0.05,p0.01,p0.05),HDL-C显著增加(p0.05)。4、8周规律游泳运动后各组大鼠Calpain2和ATG7表达水平的变化:与C组大鼠相比,H组大鼠肝脏组织Calpain2m RNA的表达量显著性增加(p0.01),ATG7m RNA的表达量显著性降低(p0.01),与H组大鼠相比,HE组大鼠肝脏组织Calpain2m RNA的表达量显著性降低(p0.01),ATG7m RNA的表达量显著性升高(p0.01)。与C组大鼠相比,H组大鼠肝脏组织Calpain2蛋白的表达显著性增加(p0.01),ATG7蛋白的表达显著性降低(p0.01),与H组大鼠相比,HE组大鼠肝脏组织Calpain2蛋白的表达显著性降低(p0.01),ATG7蛋白的表达显著性升高(p0.05)。5、8周规律游泳运动后各组大鼠IRS-1和AKT表达水平的变化:与C组大鼠相比,H组大鼠肝脏组织IRS-1m RNA的表达量显著性降低(p0.01),与H组大鼠相比,HE组大鼠肝脏组织IRS-1m RNA的表达量显著性升高(p0.01)。与C组大鼠相比,H组大鼠肝脏组织IRS-1(ser307)的磷酸化程度显著升高(p0.01),AKT(ser473)的磷酸化程度显著降低(p0.01)。与H组大鼠相比,HE组大鼠肝脏组织IRS-1(ser307)的磷酸化程度显著降低(p0.01),AKT(ser473)的磷酸化程度显著升高(p0.01)。研究结论:1、8周高脂喂养成功建立大鼠IR模型。2、8周规律游泳运动有效的预防胰岛素抵抗。3、8周规律游泳运动改善IR的可能机制:8周90min运动可以通过抑制Calpain2的表达,上调ATG7的表达,使IRS-1表达增加,从而增强PI3K/AKT信号转导,最终缓解高脂饮食诱发的IR。
[Abstract]:Insulin resistance (Insulin Resistance IR) refers to the insulin signal transduction is weakened or blocked, making the insulin physiological function weakened, resulting in insulin sensitive tissues (liver, skeletal muscle, fat) on glucose uptake and utilization of lower efficiency. Research on dietary structure is considered to be unreasonable, especially the high fat diet, and sedentary the way of life,.Calpain2 is an important cause of IR in normal circumstances only trace expression in pathological conditions of abnormal increase of.ATG7 is the expression of autophagy related genes involved in lipid metabolism, a number of studies have demonstrated that the abnormal increase of Calpain2 will decrease the expression of ATG7, interference of the insulin signal transduction pathway. As a kind of exercise effective non drug prevention and treatment, research shows that exercise can effectively reduce the expression of Calpain2 and delay the occurrence of IR, but its mechanism is not yet fully This paper aims to clarify. Therefore, high fat diet induced rat IR model, using Calpain2/ATG7 as the starting point, to investigate the effect of Calpain2/ATG7 mediated movement of the high fat diet rats IR extremely relevant mechanisms. Objective: To investigate the intervention effect and Calpain2 movement of the high fat diet rats insulin resistance the role of ATG7 in insulin resistance exercise intervention in the analysis of the movement to improve the possible mechanism of insulin resistance. To provide more scientific theory basis for the prevention and treatment of insulin resistance. Methods: 30 SD rats were randomly divided into 3 groups: 1, normal diet control group (group C). 2, high fat diet IR model group (H group), high fat diet, 3 IR model group (HE group). After 8 weeks of high fat diet (22% calories than for protein, 45% fat, 33% carbohydrate, energy is about 5305Kcal/ 1000g) feeding rat IR The model, at the same time the implementation of swimming exercise on rats. The comprehensive utilization of body weight, fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance index (HOMA-IR), insulin sensitivity index (ISI) establishment and evaluation of animal model of exercise intervention effect; through the observation of exercise on high fat diet induced liver IR Calpain2, rat ATG7, IRS-1, p-IRS-1 (Ser307), AKT, p-AKT (ser473) protein expression and expression analysis of movement of IR rat liver tissue Calpain2/ATG7 and classical IR signaling pathway related factors on high fat diet induced insulin resistance in Calpain2/ATG7. To explore the role in the process and the role of sports. Results: the evaluation of 1,8 weeks of high fat diet to establish IR rat animal model: compared with C rats, H rats in group FINS and HOMA-IR were significantly increased (P0.01, P0.01), ISI decreased significantly (P0.01). There was no significant difference in FBG rats (P0.05). 涓嶩缁勫ぇ榧犵浉姣，

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