AR阻断剂对运动骨骼肌ERK1/2信号通路的影响

Effects of AR Inhibitor on ERK1/2 Pathway of Exercise Skeletal Muscle in Rats

目的:通过阻断AR,以探讨雄激素对运动骨骼肌ERK1/2通路的影响特点。方法:7周龄雄性SD大鼠30只,随机分为对照组、AR阻断剂组、运动组、AR阻断剂运动组、假手术组。AR阻断剂组于颈部皮下包埋氟他胺释缓剂,运动组进行10 d中等强度运动,于末次运动后6 h取趾长伸肌进行指标测定。结果:与对照组相比,AR阻断剂组趾长伸肌湿重、肌纤维横截面积、AR mRNA及p-ARSer210均显著下降(p<0.01-0.05),MEK1/2、ERK1/2、P90RSK的mRNA及蛋白磷酸化水平未有显著变化。运动组AR及ERK1/2通路的mRNA及蛋白磷酸化水平则显著增加(p<0.05),而其趾长伸肌湿重、肌纤维横截面积并未有显著变化。AR阻断剂运动组各指标与运动组相比均显著下降(p<0.01-0.05),而与AR阻断剂组相比均未有显著变化。结论:阻断AR可显著抑制运动骨骼肌湿重、横截面积及AR的基因和磷酸化表达,证实雄激素对运动骨骼肌的促蛋白合成作用主要经AR介导;AR阻断剂可显著抑制运动骨骼肌ERK1/2通路激活,提示雄激素经AR介导发挥非基因作用。该研究对雄激素促进运动骨骼肌蛋白合成的非基因作用提供一定实验依据。

Objective： The purpose of this study was to investigate the effects of androgen on ERK1 /2 pathway in exercise skeletal muscle through blocking AR. Methods： Thirty seven-week old male SD rats were randomly divided into control group,AR inhibitor group,exercise group,AR inhibitor ＋ exercise group and sham group. AR inhibitor group rats were implanted subcutaneously with a flutamide release pellet,and exercise group rats participated in 10 days moderate intensity exercise. Extensor Digitorum Longus（ EDL） was isolated at 6 h after the last exercise. Results： Compared with control group,the wet weight and CSA of EDL,AR mRNA and p-AR^Ser210 in AR inhibitor group were significantly decreased（ Ps〈 0. 05）,and the mRNA and phosphorylation level of MEK1 /2,ERK1 /2 and p90 ^RSK had no significant changes. The mRNA and phosphorylation level of AR,ERK1 /2 pathway in exercise group significantly raised（ P 〈0. 05）,while the wet weight and CSA of EDL had no significant changes. All indexes in AR inhibitor ＋ exercise group were lower than in exercise group（ Ps〈 0. 05）,but had no differences compared with AR inhibitor group. Conclusions： AR inhibitor can significantly inhibit the expressions of wet weight,CSA,AR mRNA and phosphorylation of EDL,which demonstrated that the promotion of androgen on exercise skeletal muscle is mediated by AR. AR inhibitor can significantly inhibit ERK1 /2 pathway,which indicated that androgen activating ERK1 /2 pathway in exercise skeletal muscle is mediated by AR.