本文選題：胰島素抵抗　切入點(diǎn)：運(yùn)動　出處：《上海師范大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：胰島素抵抗(Insulin Resistance,IR)是指由于胰島素信號轉(zhuǎn)導(dǎo)減弱或受阻,使得胰島素生理作用減弱,進(jìn)而導(dǎo)致胰島素敏感組織(肝臟、骨骼肌、脂肪)對葡萄糖攝取和利用的效能降低。研究認(rèn)為不合理的膳食結(jié)構(gòu),特別是高脂膳食,加上久坐不運(yùn)動的生活方式,是引起IR的重要原因。Calpain2一般在正常生理情況下微量表達(dá),只有在病理情況下異常升高。ATG7是自噬相關(guān)基因參與脂代謝的表達(dá),大量研究證實(shí),Calpain2的異常升高會引起ATG7的表達(dá)下降,干擾胰島素信號轉(zhuǎn)導(dǎo)通路。運(yùn)動作為一種有效的非藥物防治手段,研究表明,運(yùn)動可有效地降低Calpain2的表達(dá)而延緩IR的發(fā)生,但其具體作用機(jī)制尚未完全闡明。因此,本文旨在以高脂飲食喂養(yǎng)誘導(dǎo)大鼠產(chǎn)生IR為模型,以Calpain2/ATG7為切入點(diǎn),探討Calpain2/ATG7介導(dǎo)運(yùn)動對高脂飲食大鼠IR的影響極其相關(guān)機(jī)制。研究目的:本研究探討運(yùn)動對高脂飲食大鼠胰島素抵抗的干預(yù)作用及Calpain2通過ATG7在運(yùn)動干預(yù)胰島素抵抗中的作用,分析運(yùn)動改善胰島素抵抗的可能機(jī)制。為預(yù)防和治療胰島素抵抗提供更科學(xué)的理論依據(jù)。研究方法:以30只SD大鼠為實(shí)驗(yàn)對象,隨機(jī)分為3組:○1普通飲食對照組(C組),○2高脂飲食IR模型組(H組),○3高脂飲食IR模型運(yùn)動組(HE組)。通過8周高脂飼料(熱卡比為蛋白質(zhì)22%,脂肪45%,碳水化合物33%,提供能量約為5305Kcal/1000g)喂養(yǎng)建立大鼠IR模型,同時對大鼠實(shí)施無負(fù)重游泳運(yùn)動干預(yù)。綜合利用體重、空腹血糖(FBG)、空腹胰島素(FINS)、胰島素抵抗指數(shù)(HOMA-IR)、胰島素敏感指數(shù)(ISI)評價動物模型的建立和運(yùn)動干預(yù)的效果;通過觀察運(yùn)動對高脂飲食誘導(dǎo)的IR大鼠肝臟ATG7、Calpain2、IRS-1、p-IRS-1(ser307)、AKT、p-AKT(ser473)蛋白的表達(dá),分析運(yùn)動對高脂飲食誘導(dǎo)IR大鼠肝臟組織Calpain2/ATG7和IR經(jīng)典信號通路相關(guān)因子的表達(dá)。探討Calpain2/ATG7在胰島素抵抗過程中的作用以及運(yùn)動在其中的作用。研究結(jié)果:1、8周高脂喂養(yǎng)建立大鼠IR動物模型的評價:與C組大鼠相比,H組大鼠的FINS和HOMA-IR均顯著升高(p0.01,p0.01),ISI顯著降低(p0.01)。大鼠FBG無顯著性差異(p0.05)。與H組大鼠相比,HE組大鼠的FINS和HOMA-IR均顯著降低(p0.05,p0.01),ISI顯著增加(p0.01)。大鼠FBG無顯著性差異(p0.05)。2、各組大鼠體重的變化:實(shí)驗(yàn)前各組大鼠體重?zé)o顯著性差異(p0.05)。實(shí)驗(yàn)期間大鼠飼養(yǎng)條件良好毛色光亮,生長發(fā)育正常。8周實(shí)驗(yàn)后,H組大鼠體重顯著高于C組(p0.01),HE組大鼠體重顯著低于H組大鼠(p0.01),HE組大鼠體重與C組大鼠體重?zé)o顯著差異(p0.05)。3、8周規(guī)律游泳運(yùn)動后各組大鼠血脂的變化:與C組大鼠相比,H組大鼠的TG、TC、LDL-C均顯著升高(p0.05,p0.05,p0.01),HDL-C顯著降低(p0.05)。與H組大鼠的血脂相比,HE組大鼠的TG、TC、LDL-C均顯著降低(p0.05,p0.01,p0.05),HDL-C顯著增加(p0.05)。4、8周規(guī)律游泳運(yùn)動后各組大鼠Calpain2和ATG7表達(dá)水平的變化:與C組大鼠相比,H組大鼠肝臟組織Calpain2m RNA的表達(dá)量顯著性增加(p0.01),ATG7m RNA的表達(dá)量顯著性降低(p0.01),與H組大鼠相比,HE組大鼠肝臟組織Calpain2m RNA的表達(dá)量顯著性降低(p0.01),ATG7m RNA的表達(dá)量顯著性升高(p0.01)。與C組大鼠相比,H組大鼠肝臟組織Calpain2蛋白的表達(dá)顯著性增加(p0.01),ATG7蛋白的表達(dá)顯著性降低(p0.01),與H組大鼠相比,HE組大鼠肝臟組織Calpain2蛋白的表達(dá)顯著性降低(p0.01),ATG7蛋白的表達(dá)顯著性升高(p0.05)。5、8周規(guī)律游泳運(yùn)動后各組大鼠IRS-1和AKT表達(dá)水平的變化:與C組大鼠相比,H組大鼠肝臟組織IRS-1m RNA的表達(dá)量顯著性降低(p0.01),與H組大鼠相比,HE組大鼠肝臟組織IRS-1m RNA的表達(dá)量顯著性升高(p0.01)。與C組大鼠相比,H組大鼠肝臟組織IRS-1(ser307)的磷酸化程度顯著升高(p0.01),AKT(ser473)的磷酸化程度顯著降低(p0.01)。與H組大鼠相比,HE組大鼠肝臟組織IRS-1(ser307)的磷酸化程度顯著降低(p0.01),AKT(ser473)的磷酸化程度顯著升高(p0.01)。研究結(jié)論:1、8周高脂喂養(yǎng)成功建立大鼠IR模型。2、8周規(guī)律游泳運(yùn)動有效的預(yù)防胰島素抵抗。3、8周規(guī)律游泳運(yùn)動改善IR的可能機(jī)制:8周90min運(yùn)動可以通過抑制Calpain2的表達(dá),上調(diào)ATG7的表達(dá),使IRS-1表達(dá)增加,從而增強(qiáng)PI3K/AKT信號轉(zhuǎn)導(dǎo),最終緩解高脂飲食誘發(fā)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). 涓嶩緇勫ぇ榧犵浉姣，

本文編號：1589668