雄激素受体在抗阻和耐力训练提高大鼠运动能力中的作用及机制

发布时间：2018-05-28 14:09

本文选题：AR + 氟他胺　；参考：《上海体育学院》2017年硕士论文

【摘要】：研究目的:雄激素与雄激素受体(androgen receptor,AR)结合后有促进肌肉蛋白质合成、增加肌肉质量和提高肌肉力量的作用,但其作用机制仍未明确。本课题以SD雄性大鼠为研究对象,利用AR阻断剂Flutamine(氟他胺)研究AR对安静和运动大鼠运动能力的影响及其机制-是否与胰岛素样生长因子1(insulin growth factor 1,IGF-1)/磷脂酰肌醇3激酶(phosphoinositide 3-kinase,PI3K)/Akt/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)通路有关?研究方法:48只SD雄性大鼠(7周龄)随机分为6组,每组8只:安静对照组(C)、氟他胺组(F)、抗阻训练组(R)、抗阻训练+氟他胺组(R+F)、耐力训练组(E)和耐力训练+氟他胺组(E+F)。实验前将氟他胺21天缓释剂(50 mg/片)包埋于F、R+F和E+F组大鼠的颈部皮下。C组和F组大鼠不进行运动训练,而E、E+F组大鼠进行中等强度(速度20 m/min)的跑台耐力训练,R、R+F组大鼠进行递增负荷的爬梯抗阻训练,均为每周训练6天,持续3周。最后一次训练后36 h,检测所有大鼠的体重、力量(最大抓力和启动时最大负重分别反映最大力量和速度力量)和耐力(一次力竭运动时间)。在力竭运动结束36 h后,麻醉大鼠,下腔静脉取血。之后,处死大鼠,取腓肠肌、比目鱼肌。ELISA方法检测血清IGF-1水平;蒽酮法检测骨骼肌的肌糖原含量,real time PCR检测骨骼肌IGF-1R和m TOR的m RNA水平;Western blot检测骨骼肌的AR、IGF-1、IGF-1R、m TOR、PI3K、肌球蛋白重链(Myosin heavy chain,MHC)、快肌球蛋白(fs-myosin)和慢肌钙蛋白(ss-Tn T)的蛋白水平,以及PI3K和Akt的表达和活性。研究结果:1.AR介导安静和抗阻训练大鼠体重的增加,但耐力训练所致大鼠体重的减轻与AR无关氟他胺不仅降低安静对照组大鼠的体重(p0.01),还降低抗阻训练大鼠的体重(p0.05),但对耐力训练所致大鼠体重的减轻无显著影响(p0.05)。2.AR介导抗阻训练所致大鼠最大力量和速度力量的增加,但耐力训练增加耐力的作用与AR无关抗阻训练而不是耐力训练显著增加大鼠的最大力量(最大抓力/体重比值)和速度力量(启动时最大负重)(p0.05),且该作用被氟他胺逆转(p0.05)。而耐力训练增加大鼠耐力的作用(p0.05)不能被AR减弱,表明其与AR无关。3.抗阻训练大鼠腓肠肌和耐力训练大鼠比目鱼肌相对重量的增加是通过AR介导的抗阻训练增加中间态肌腓肠肌的相对重量(p0.05),且该作用被氟他胺逆转(p0.01),但对比目鱼肌的相对重量无影响。而耐力训练增加慢肌比目鱼肌的相对重量(p0.05),且该作用被氟他胺逆转(p0.01),但对腓肠肌的相对重量无影响。4.抗阻训练通过AR介导大鼠腓肠肌快肌纤维的增多,而耐力训练大鼠比目鱼肌慢肌纤维的增多与AR无关抗阻运动增加腓肠肌快肌特异性蛋白fs-myosin的含量(p0.05),对慢肌特异性蛋白ss Tn T无显著作用;抗阻运动增加腓肠肌fs-myosin含量的作用被氟他胺逆转(p0.01)。而耐力训练增加比目鱼肌ss Tn T的含量(p0.05),但对fs-myosin含量无显著作用。耐力训练增加比目鱼肌ss Tn T含量的作用不被氟他胺减轻。5.抗阻训练大鼠腓肠肌和耐力训练大鼠比目鱼肌MHC含量的增加是通过AR介导的抗阻训练增加大鼠腓肠肌的MHC蛋白水平(p0.05),耐力训练增加比目鱼肌的MHC蛋白水平(p0.05),且运动引起的MHC蛋白水平增加的作用都能被氟他胺所逆转(p0.01)。6.抗阻和耐力运动引起的大鼠腓肠肌和比目鱼肌肌糖原含量的增加是通过AR介导的与安静对照大鼠相比,抗阻和耐力训练都能显著增加腓肠肌和比目鱼肌的肌糖原含量(p0.01),而运动增加肌糖原含量的作用被氟他胺逆转(p0.01)。7.抗阻训练大鼠腓肠肌和耐力训练大鼠比目鱼肌IGF-1R/m TOR通路信号分子的增加通过AR介导,而抗阻和耐力训练不影响血清IGF-1水平抗阻训练显著增加腓肠肌、耐力训练显著增加比目鱼肌的IGF-1R和m TOR的m RNA水平(均p0.05),且该作用都能被氟他胺逆转(p0.01,p0.05)。对于蛋白水平,抗阻训练增加腓肠肌IGF-1(p0.05)、IGF-1R(p0.01)和m TOR(p0.05)的蛋白水平,该作用被氟他胺逆转(p0.05,p0.01,p0.01);而耐力训练增加比目鱼肌IGF-1(p0.01)和IGF-1R(p0.05)蛋白水平,该作用被氟他胺逆转;此外,氟他胺降低降低比目鱼肌的m TOR(p0.05)蛋白水平。此外,尽管抗阻和耐力训练未影响血清IGF-1的水平,以及耐力训练不影响比目鱼肌的m TOR的蛋白水平,但上述指标均能被氟他胺降低。8.抗阻训练大鼠腓肠肌和耐力训练大鼠比目鱼肌PI3K和Akt的表达和活性的增加是AR介导的抗阻训练增加腓肠肌、耐力训练增加比目鱼肌的PI3K和Akt的活性(p-PI3K/PI3K、p-Akt/Akt的比值)(均p0.05),该作用被氟他胺逆转(均p0.05)。结论1.抗阻训练通过AR介导大鼠最大力量和速度力量的增强,而耐力训练提高耐力的作用可能与AR无关。2.抗阻训练通过AR介导大鼠力量增强的机制与其增加腓肠肌的相对重量、快肌纤维含量、内在收缩力和肌糖原含量有关。3.耐力训练通过AR介导比目鱼肌相对重量、内在收缩力和肌糖原含量的增加,但其增加慢肌纤维的作用不是通过AR介导。这可能是AR阻断剂在降低比目鱼肌相对重量、收缩力和肌糖原含量的情况下没有降低大鼠耐力的可能机制之一,但仍需进一步证实。4.抗阻训练增加腓肠肌、耐力训练增加比目鱼肌相对重量的机制与运动激活肌肉AR,进而激活IGF-1/IGF-1R-PI3K/Akt-m TOR信号通路有关。但是,训练通过AR的介导如何增加快肌纤维含量、MHC水平和肌糖原含量,仍待研究。
[Abstract]:Objective: the combination of androgen and androgen receptor (androgen receptor, AR) can promote muscle protein synthesis, increase muscle mass and improve muscle strength, but its mechanism is still not clear. This subject takes SD male rats as the research object, and uses the AR blocker Flutamine (fluretamine) to study the exercise of AR on the exercise of quiet and exercise rats. The effect of ability and its mechanism - is it related to the insulin like growth factor 1 (insulin growth factor 1, IGF-1) / phosphatidyl inositol 3 kinase (phosphoinositide 3-kinase, PI3K) /Akt/ mammal rapamycin target protein (mammalian target of rapamycin) pathway? Methods: 48 male rats (7 weeks of age) were randomly divided into 6 groups, each Group 8: quiet control group (C), flualamine group (F), resistance training group (R), resistance training + flutamide group (R+F), endurance training group (E) and endurance training + flutamide group (E+F). Before experiment, the 21 day slow-release flualamines (50 mg/ tablets) were embedded in F, R+F and E+F group rats' neck subcutaneous.C group and F group rats were not exercise. Medium strength (speed 20 m/min) endurance training, R and R+F rats were trained for incremental load of climbing ladder resistance training for 6 days a week for 3 weeks. After the last training, 36 h was used to detect the weight of all rats. Strength (maximum grasp and maximum weight reflected the maximum strength and speed strength) and endurance (one exhaustion). Exercise time). After the exhaustion movement ended 36 h, the rats were anesthetized and the inferior vena cava was taken blood. After that, the rats were killed, the gastrocnemius muscle, the soleus muscle and the.ELISA method were used to detect the serum IGF-1 level. The content of the skeletal muscle glycogen was detected by the anthrone method, and the real time PCR was used to detect the m RNA level of the skeletal muscle IGF-1R and m TOR. 1R, m TOR, PI3K, myosin heavy chain (Myosin heavy chain, MHC), the protein levels of fast myosin (fs-myosin) and slow troponin (ss-Tn T), as well as the expression and activity of PI3K and ss-Tn. The weight (P0.01) of the rats in the low quiet control group and the weight of the resistance training rats (P0.05) had no significant effect on the weight loss of rats induced by endurance training (P0.05).2.AR mediated the increase of maximum strength and speed of rats induced by resistance training, but endurance training was not related to AR, but not endurance training, not endurance. Training significantly increased the maximum strength (maximum grip / weight ratio) and speed strength (P0.05), and the effect was reversed by flutamide (P0.05). The effect of endurance training increased rat endurance (P0.05) could not be weakened by AR, indicating that it was not related to AR in the gastrocnemius and endurance training rat soleus with.3. resistance training. The increase in relative weight of the muscle increased the relative weight of the meso gastrocnemius by AR mediated resistance training (P0.05), and the effect was reversed by flutamide (P0.01), but had no effect on the relative weight of the soleus muscle. Endurance training increased the relative weight of the slow soleus muscle (P0.05), and the effect was reversed by flutamide (P0.01), but to the gastrocnemius. The relative weight of the muscle did not affect the increase of the.4. resistance training through AR, while the increase of the slow muscle fiber in the endurance training rat and the AR independent resistance exercise increased the content of the fast muscle specific protein fs-myosin of the gastrocnemius muscle (P0.05), and had no significant effect on the slow muscle specific protein SS Tn T, and the resistance exercise increased. The effect of fs-myosin content of gastrocnemius was reversed by flutamide (P0.01). Endurance training increased the content of SS Tn T in soleus muscle (P0.05), but had no significant effect on fs-myosin content. The effect of endurance training to increase the content of SS Tn T in soleus muscle was not reduced by flutamide in reducing the MHC content of the gastrocnemius and endurance training rat soleus muscle of.5. resistance training rats. The increase in AR mediated resistance training increases the MHC protein level (P0.05) of the gastrocnemius muscle in rats and the endurance training increases the MHC protein level of the soleus muscle (P0.05), and the effect of the increase of MHC protein in the exercise can be caused by the reverse (P0.01).6. resistance and endurance exercise of the gastrocnemius and soleus muscle glycogen caused by the exercise of the resistance and endurance exercise of the (P0.01).6.. The increase in content is that resistance and endurance training can significantly increase the content of muscle glycogen (P0.01) in the gastrocnemius and soleus muscle by AR mediated resistance and endurance training, while the action of increasing the content of muscle glycogen in the exercise is the IGF-1R/m TOR pathway of the gastrocnemius and the endurance training rat of P0.01.7. resistance training. The increase of signal molecules was mediated by AR, while resistance and endurance training did not affect the sera IGF-1 level resistance training significantly increasing the gastrocnemius muscle, endurance training significantly increased the m RNA level of IGF-1R and m TOR of the soleus muscle (P0.05), and the effect could be reversed by flutamide (P0.01, P0.05). For protein level, resistance training increased the IGF-1 gastrocnemius muscle (P0.05) the protein levels of IGF-1R (P0.01) and m TOR (P0.05), which were reversed by fluamamines (P0.05, P0.01, P0.01), and endurance training increased the level of IGF-1 (P0.01) and IGF-1R protein in the soleus, and the effect was reversed by flutamide; in addition, flutamide decreased the protein level of the soleus muscle. In addition, resistance and endurance, in spite of resistance and endurance. The training did not affect the level of serum IGF-1, and endurance training did not affect the protein level of M TOR in the soleus muscle, but the above indexes could be reduced by fluamamines to decrease the expression and activity of PI3K and Akt in the gastrocnemius and endurance training rats of.8. resistance training. The increase of the gastrocnemius muscle and endurance training increased by AR mediated resistance training. The activity of PI3K and Akt in soleus muscle (the ratio of p-PI3K/PI3K, p-Akt/Akt) (both P0.05), the effect was reversed by flutamide (all P0.05). Conclusion 1. resistance training is mediated by AR to enhance the strength and strength of the rats' maximum strength and speed, and the effect of endurance training to improve endurance may be associated with AR independent.2. resistance training through AR mediated rat strength enhancement machine. The relative weight of the gastrocnemius muscle, the fast muscle fiber content, the intrinsic contractile force and the muscle glycogen content related.3. endurance training through AR mediate the relative weight of the soleus, the internal contractile force and the muscle glycogen content, but the effect of the increase of the slow muscle fiber is not mediated by the AR. This may be that the AR blocker is relative to the soleus muscle. Weight, contractile force and muscle glycogen content is not one of the possible mechanisms to reduce rat endurance, but it is still necessary to further confirm that.4. resistance training increases the gastrocnemius muscle, endurance training increases the relative weight mechanism of the soleus muscle, and activates the muscle AR, and then activates the IGF-1/ IGF-1R-PI3K/Akt-m TOR signaling pathway. However, training passes through How AR mediates rapid muscle fiber content, MHC level and muscle glycogen content remains to be studied.
【学位授予单位】：上海体育学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：G804.2

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