本文選題：孤核受體 + 運動��； 參考：《華東師范大學(xué)》2010年碩士論文

【摘要】： 目前,心血管疾病居全球成人死因的首位；全球有2.46億人被確診為糖尿病,并預(yù)測到2025年全球糖尿病人數(shù)將超過3.8億；癌癥的每年新增病例數(shù)約為800萬,死亡數(shù)約為620萬；心血管疾病、癌癥、糖尿病等正成為威脅人類健康的“頭號殺手”。 很多學(xué)者一直致力于這些疾病的發(fā)病機理和防治工作的研究,隨著研究的深入,發(fā)現(xiàn)核受體不僅對機體的生長、發(fā)育、正常生理功能的維持和代謝過程起著重要的調(diào)節(jié)作用,而且與多種疾病如乳腺癌、前列腺癌、糖尿病及肥胖的發(fā)生、發(fā)展有直接關(guān)聯(lián)。核受體成為疾病病理研究這一領(lǐng)域的一個重點。 雞卵白蛋白上游啟動子轉(zhuǎn)錄因子家族(COUP-TFs)是屬于核受體中孤核受體家族的一員,有COUP-TFⅠ和COUP-TFⅡ兩個亞型,它們在組織中廣泛表達(dá),與多種基因的轉(zhuǎn)錄相關(guān),在器官形成、神經(jīng)發(fā)生、細(xì)胞分化等方面有重要的作用。COUP-TFs的突變或異常表達(dá)與人類的先天性心臟病、糖尿病和癌癥等疾病相關(guān)。特別是COUP-TFⅡ基因在骨骼、肌肉、脂肪形成與代謝平衡中起調(diào)節(jié)作用。 目的：比較研究一次性急性運動、高強度間歇性沖刺訓(xùn)練、耐力訓(xùn)練對SD大鼠及耐力訓(xùn)練對GK大鼠骨骼肌中COUP-TFⅠ和COUP-TFⅡ基因表達(dá)的的影響,探討機體運動適應(yīng)中糖代謝與COUP-TFⅠ、COUP-TFⅡ基因表達(dá)的變化關(guān)系。 方法：將40只雄性SD大鼠,4周齡,體重100±5g；12只GK大鼠,8周齡,體重250±5g,SD大鼠隨機分成SD對照組(C)、SD急性耐力訓(xùn)練組(D)、SD耐力訓(xùn)練組(E)、SD間歇性沖訓(xùn)練組(S),每組10只；GK大鼠隨機分成GK對照組(H)、GK耐力訓(xùn)練組(R),每組6只。急性耐力訓(xùn)練：大鼠1-6周與安靜組飼養(yǎng)方式相,處死前進行一次急性耐力訓(xùn)練,起始跑速為13m/min,最大速度不超過16.7m/min,訓(xùn)練時間60min；間歇性沖刺訓(xùn)練：每天3組,每組3次,每次10s極量強度(≥50m/min)的跑臺運動,每次間歇時間30-60s,組間間歇時間3min；耐力訓(xùn)練：持續(xù)6周的跑臺訓(xùn)練,起始跑速為13m/min,最大速度不超過16.7m/min,前2周每次訓(xùn)練40分鐘,后4周每次訓(xùn)練60min,每周訓(xùn)練6天。所有大鼠6周飼養(yǎng)后處死,酶標(biāo)儀檢測血糖、血漿胰島素、血漿脂聯(lián)素、糖化血紅蛋白和糖化血清蛋白。采用實時熒光定量PCR法檢測COUP-TFⅠ和COUP-TFⅡ基因轉(zhuǎn)錄水平,Western Blotting檢測COUP-TFⅠ蛋白表達(dá)水平。 結(jié)果： (1)三種不同運動方式對SD大鼠體重增長及耐力訓(xùn)練對GK大鼠體重增長無顯著影響。 (2)耐力訓(xùn)練能夠顯著降低SD大鼠安靜時的血糖水平,但對胰島素抵抗指數(shù)無顯著影響；耐力訓(xùn)練能顯著降低GK大鼠血糖及胰島素抵抗指數(shù)。 (3)三種不同的運動方式能顯著降低SD大鼠糖化血清蛋白含量；耐力訓(xùn)練能極顯著降低GK大鼠糖化血清蛋白。 (4)耐力訓(xùn)練能夠顯著升高SD大鼠與GK大鼠血脂聯(lián)素濃度。 (5)一次性急性運動與耐力訓(xùn)練能顯著上調(diào)SD大鼠骨骼肌中COUP-TFⅠmRNA;耐力訓(xùn)練能顯著下調(diào)GK大鼠骨骼肌中COUP-TFⅠmRNA表達(dá)。 (6)一次性急性運動、耐力訓(xùn)練、高強度間歇性沖刺訓(xùn)練對SD大鼠COUP-TFⅠ蛋白表達(dá)無顯著影響；耐力訓(xùn)練能極顯著降低GK大鼠COUP-TFⅠ蛋白表達(dá)。 (7)一次性急性運動、耐力訓(xùn)練、高強度間歇性沖刺訓(xùn)練能顯著下調(diào)SD大鼠骨骼肌中COUP-TFⅡmRNA表達(dá)；耐力訓(xùn)練能顯著下調(diào)GK大鼠COUP-TFⅡmRNA水平 結(jié)論： (1)耐力訓(xùn)練有利于GK大鼠血糖降低水平,改善胰島素抵抗。 (2)急性運動、耐力訓(xùn)練、沖刺訓(xùn)練可使導(dǎo)致SD大鼠骨骼肌中COUP-TFⅠmRNA水平上升,COUP-TFⅡmRNA表達(dá)水平下降,而這三種運動對COUP-TFⅠ蛋白表達(dá)水平無顯著影響,表現(xiàn)出與COUP-TFⅠmRNA水平變化不一致。說明COUP-TFⅠ和COUP-TFⅡ在基因轉(zhuǎn)錄水平參與了骨骼肌對急性耐力運動的快速應(yīng)答,也參與了骨骼肌對長期耐力訓(xùn)練、間歇性大強度訓(xùn)練的慢性適應(yīng)。運動可能傾向于激活骨骼肌COUP-TFⅠ基因表達(dá),并抑制COUP-TFⅡ基因表達(dá)。 (3)長期耐力訓(xùn)練改善GK大鼠胰島素抵抗可能與骨骼肌COUP-TFⅠ基因、蛋白表達(dá)以及COUP-TFⅡ基因表達(dá)下調(diào)有關(guān)。 (4)在正常生理和糖尿病病理條件下,耐力運動對骨骼肌COUP-TFⅠ基因表達(dá)有著決然相反的影響；考慮到GK大鼠與SD大鼠的品系、年齡、飲食差異,本實驗不能排除以上因素對耐力運動效應(yīng)的影響。 (5)與COUP-TF相比,在正常生理和糖尿病病理條件下,COUP-TFⅡ基因表達(dá)對耐力運動的適應(yīng)特征完全一致,表明耐力運動對COUP-TFⅡ基因表達(dá)的抑制在胰島素抵抗的預(yù)防和改善中可能發(fā)揮更重要的作用。
[Abstract]:At present, cardiovascular disease ranks first in the world's cause of death; 246 million people worldwide have been diagnosed with diabetes, and it is predicted that the number of global diabetes will exceed 380 million by 2025; the number of new cases of cancer is about 8 million a year, and the number of deaths is about 6 million 200 thousand; cardiovascular disease, cancer, diabetes and so on are becoming the "No. 1" killing of human health. Hand.
Many scholars have been working on the pathogenesis and prevention and treatment of these diseases. With the further research, it is found that the nuclear receptor not only plays an important role in the growth and development of the body, the maintenance of normal physiological function and the metabolic process, but also develops and develops with a variety of diseases such as breast cancer, prostate cancer, diabetes and obesity. There is a direct correlation. Nuclear receptors have become a focus in the field of pathological research.
The chicken oocyte albumin upstream promoter transcription factor family (COUP-TFs) is a member of the nucleus receptor family of the nuclear receptor. There are two subtypes of COUP-TF I and COUP-TF II. They are widely expressed in the tissues, related to the transcription of a variety of genes, and have an important role in the mutation of.COUP-TFs in organogenesis, neurogenesis, and cell differentiation. Abnormal expression is associated with human congenital heart disease, diabetes and cancer. In particular, the COUP-TF II gene plays a regulatory role in bone, muscle, fat formation and metabolic balance.
Objective: To compare the effects of SD rats and endurance training on the expression of COUP-TF I and COUP-TF II gene in skeletal muscles of GK rats and the relationship between the metabolism of glucose and the expression of COUP-TF I and COUP-TF II in the exercise adaptation.
Methods: 40 male SD rats, 4 weeks old, weight 100 5g, 12 GK rats, 8 weeks old and 250 + 5g, were randomly divided into SD control group (C), SD acute endurance training group (D), SD endurance training group (E), 10 rats in each group, 6 rats in each group. Practice: 1-6 weeks of rats with the quiet group feeding mode, before the death of an acute endurance training, the starting speed is 13m/min, the maximum speed is not more than 16.7m/min, training time 60min, intermittent sprint training: 3 groups of 3 times each day, each time 10s maximum intensity (> 50m/min) of the run, each interval time 30-60s, intermission time of 3 Min; endurance training: a 6 week running platform training with a starting speed of 13m/min, the maximum speed of not exceeding 16.7m/min, the first 2 weeks of training of 40 minutes, each training 60min for the first 4 weeks and 6 days of training every week. All rats were sacrificed after 6 weeks of feeding, and the enzyme was used to detect blood glucose, plasma insulin, plasma adiponectin, glycated hemoglobin and glycosylated serum protein. The transcriptional levels of COUP-TF I and COUP-TF II genes were detected by real-time fluorescence quantitative PCR. The expression level of COUP-TF I protein was detected by Western Blotting.
Result:
(1) three different exercises had no significant effect on weight gain and endurance training of SD rats on weight gain of GK rats.
(2) endurance training could significantly reduce the level of blood glucose in SD rats, but had no significant effect on the insulin resistance index, and endurance training could significantly reduce the blood glucose and insulin resistance index in GK rats.
(3) three different ways of exercise can significantly reduce the content of glycated serum protein in SD rats; endurance training can significantly reduce glycated serum protein in GK rats.
(4) endurance training can significantly increase the level of adiponectin in SD rats and GK rats.
(5) one time acute exercise and endurance training can significantly increase the COUP-TF I mRNA in the skeletal muscles of SD rats, and endurance training can significantly reduce the expression of COUP-TF I mRNA in the skeletal muscles of GK rats.
(6) one time acute exercise, endurance training, and high intensity intermittent sprint training had no significant effect on the expression of COUP-TF I protein in SD rats; endurance training could significantly reduce the expression of COUP-TF I protein in GK rats.
(7) one time acute exercise, endurance training, and high intensity intermittent sprint training can significantly reduce the expression of COUP-TF II mRNA in the skeletal muscle of SD rats; endurance training can significantly reduce the level of COUP-TF II mRNA in GK rats
Conclusion:
(1) endurance training is beneficial to lowering blood glucose level and improving insulin resistance in GK rats.
(2) acute exercise, endurance training and sprint training could increase the level of COUP-TF I mRNA in the skeletal muscles of SD rats and decrease the expression level of COUP-TF II mRNA, and the three kinds of exercise had no significant influence on the expression level of COUP-TF I protein, which showed that the level of COUP-TF I mRNA was not consistent with the level of COUP-TF I mRNA. With the rapid response of skeletal muscle to acute endurance exercise, it also participates in the chronic adaptation of skeletal muscle to long-term endurance training and intermittent large intensity training. Exercise may tend to activate the expression of COUP-TF I gene in skeletal muscle and inhibit the expression of COUP-TF II gene.
(3) long-term endurance training can improve insulin resistance in GK rats, which may be related to the down regulation of COUP-TF I gene, protein expression and COUP-TF II gene expression in skeletal muscle.
(4) in normal physiological and diabetic pathological conditions, endurance exercise has the opposite effect on the expression of COUP-TF I gene in skeletal muscle. Considering the strain, age, and dietary differences of GK rats and SD rats, this experiment can not exclude the effects of the above factors on the endurance exercise effect.
(5) compared with COUP-TF, the adaptation characteristics of COUP-TF II gene expression to endurance exercise in normal physiological and diabetic pathological conditions show that the inhibition of COUP-TF II gene expression by endurance exercise may play a more important role in the prevention and improvement of insulin resistance.
【學(xué)位授予單位】：華東師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2010
【分類號】：R363

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