AR阻断剂对运动骨骼肌mTOR信号通路的影响

Effects of AR Inhibitor and Exercise on mTOR Pathway in Skeletal Muscle

目的:通过阻断雄激素受体(AR)并结合运动,探讨雄激素对运动骨骼肌哺乳动物雷帕霉素靶蛋白(m TOR)信号通路的影响特点。方法:30只7周龄雄性SD大鼠,适应性训练后随机分为5组:安静对照组(C)、AR阻断剂组(F)、运动组(E)、AR阻断剂运动组(EF)、假手术组(S)。F、EF组于实验前3 d颈部皮下包埋氟他胺释缓剂,E、EF组进行为期10 d的中等强度运动,于末次运动后6 h取趾长伸肌,测定肌球蛋白重链(MHC)蛋白表达及AR、m TOR、核糖体S6蛋白激酶(p70S6K)、真核起始因子4E结合蛋白(4EBP1)基因及蛋白和磷酸化表达。结果:F组体重与C组相比显著下降(P<0.01),E组无显著差异。F组MHC含量与C组相比显著下降(P<0.05),E组则显著升高(P<0.05);EF组与E组相比显著下降(P<0.01)。F组AR m RNA、p-AR与C组相比显著下降(P<0.01),E组显著升高(P<0.05),EF组与E组相比显著下降(P<0.01)。F组m TOR、p70S6K、4EBP1 m RNA与C组相比均显著下调(P<0.05,P<0.01,P<0.05),E组则显著上调(P<0.05),EF组与E组相比显著下降(P<0.01)。F组p-m TOR、p-4EBP1、4EBP1与C组相比均显著下降(P<0.01,P<0.01,P<0.05),E组p-m TOR、m TOR、p-p70S6K显著增加(P<0.01,P<0.01,P<0.05),EF组与E组相比显著下降(P<0.01)。结论:阻断AR可显著抑制m TOR通路活性,运动则促进m TOR通路活性增强,阻断AR后运动并不能诱导m TOR通路活性增强,表明雄激素对运动骨骼肌m TOR通路的作用主要经AR介导的非基因途径进行。

Objective To investigate the effects of blocking androgen receptors（AR）and exercise on androgen m TOR pathway in skeletal muscle. Methods 30 adult male SD rats were randomly divided into 5groups after adaptive training： control group（C）,AR inhibitor group（F）,exercise group（E）, AR inhibitor＋exercise group（EF） and sham group（S）. Groups F and EF were？implanted subcutaneously with a flutamide release pellet 3 days before the beginning of experiment,and groups E and EF exercised on a treadmill（20 m/min,10%,60 min/d）. After 10 days,extensor digitorum longus was isolated 6 hours after the last exercise.MHC content and protein,and phosphorylation levels of AR,m TOR,p70S6 Kand 4EBP1 were measured,and m RNA levels were evaluated. Results Compared with group C,the body weight in group F decreased significantly（P 〈 0.01）,and changed insignificantly in group E. MHC content in group F decreased significantly（P 〈 0.05）,while in group E increased significantly（P 〈 0.05）,as well as in group EF（P 〈 0.01）as compared with group E. AR m RNA and phosphorylation in group F reduced significantly（P 〈 0.01）,while increased in group E（P 〈 0.05）,as well as in group EF（P 〈 0.01） as compared with group E. Compared with C group,m TOR,p70S6 K,and 4EBP1 m RNA in group F reduced significantly（P 〈 0.05,P 〈 0.01,P 〈 0.05,respectively）,while increased significantly in group E（P 〈 0.05） and EF group（P 〈 0.01） as compared with group E. Compared with group C,p-m TOR,4EBP1 and p-4EBP1 in group F reduced significantly（P 〈 0.01,P 〈 0.01,P 〈 0.05,respectively）,p-m TOR,m TOR and p-p70S6 Kin group E increased significantly（P 〈 0.01,P 〈 0.01,P 〈 0.05,respectively）. Conclusion Blocking AR receptor inhibits and exercise promotes the activity of m TOR pathway.