中国比较医学杂志2025,Vol.35Issue(1):59-66,126,9.DOI:10.3969/j.issn.1671-7856.2025.01.006
AKT/mTOR通路介导自噬参与肩袖撕裂相关肌肉萎缩运动康复的分子机制
Molecular mechanisms of autophagy mediated by AKT/mTOR pathway in exercise rehabilitation of rotator cuff tear-related muscle atrophy
摘要
Abstract
Objective To explore the molecular mechanism of autophagy mediated by the protein kinase B(AKT)/mammalian target protein of rapamycin(mTOR)pathway in the rehabilitation of muscle atrophy associated with rotator cuff tears(RCTs).Methods Forty male C57BL/6J mice were randomly assigned to the following four groups:sham group,RCTs group,RCTs+exercise group,and RCTs+exercise+rapamycin group,with 10 mice in each group.On the eighth week after grouping,healing of the bone-tendon interface and muscle cell atrophy were analyzed by histology.The mRNA expression levels of muscle-atrophy-related genes(Atrogin-1,Bnip 3,MuRF-1)in supraspinatus muscle tissue were measured by real-time quantitative reverse transcription polymerase chain reaction.The expression of LC3 and AKT/mTOR signal pathway proteins in the supraspinatus muscle tissue of the groups was detected by Western blot,and the degree of autophagy in each group was analyzed by transmission electron microscope.Results Compared with the sham operation group,in RCTs group's maturity score for the bone-tendon interface at the supraspinatus tendon anchorage and the cross-sectional area of the supraspinatus muscle fibers decreased significantly(P<0.001),while muscle loss and the expression of Atrogin-1,Bnip 3,and MuRF-1 increased significantly(P<0.001).Compared with the RCTs group,the RCTs+exercise group showed a significant increase in bone-tendon interface maturity score and cross-sectional area of the supraspinatus muscle fibers(P<0.01)and a decrease in muscle loss and the expression of Atrogin-1,Bnip 3,and MuRF-1(P<0.01).Compared with the sham group,the RCTs group's LC3Ⅰ/LC3Ⅱ and degree of autophagy in the supraspinatus muscle increased significantly(P<0.001),while p-AKT/AKT and p-mTOR/mTOR expression decreased significantly(P<0.01).Compared with RCTs group,the RCTs+exercise group's LC3Ⅰ/LC3Ⅱ and degree of autophagy decreased significantly(P<0.01)and p-AKT/AKT and p-mTOR/mTOR expression increased significantly(P<0.001).The addition of rapamycin significantly reversed the rehabilitation effect of exercise in the RCTs group.Conclusions This study confirmed the anti-atrophy effect of exercise rehabilitation in RCT diseases and showed that its mechanism is related to AKT/mTOR signal activation,which inhibits autophagy.关键词
蛋白激酶B/哺乳动物雷帕霉素靶蛋白/肩袖撕裂/小鼠/肌肉萎缩/自噬Key words
protein kinase B/mammalian target protein of rapamycin/rotator cuff tears/mice/muscle atrophy/autophagy引用本文复制引用
唐婧,徐韦琳,刘蓉,王洪涛..AKT/mTOR通路介导自噬参与肩袖撕裂相关肌肉萎缩运动康复的分子机制[J].中国比较医学杂志,2025,35(1):59-66,126,9.基金项目
湖北省卫生健康委员会科研项目(WJ2021M039) (WJ2021M039)
武汉市医学科研项目(WX20D12). (WX20D12)