OBJECTIVE Skeletal muscle undergoes rapid and profound atrophy in response to decreased mechanical loading,e.g.,limb immobilization and bed rest.Phosphatidylinositol 3 kinase(PI3K)/Akt signaling pathway is critical fo...OBJECTIVE Skeletal muscle undergoes rapid and profound atrophy in response to decreased mechanical loading,e.g.,limb immobilization and bed rest.Phosphatidylinositol 3 kinase(PI3K)/Akt signaling pathway is critical for regulating the balance between protein synthesis and degradation during disuse/inactivity-induced muscle atrophy.The present study aimed to investigate whether natural product Icaritin(ICT)required PI3K/Akt signaling to exert counteractive effect on skeletal muscle atrophy following mechanical unloading.METHODS Two oral dosages of ICT(80and 120mg·kg-1·d-1)were administrated daily to adult male rats with or without daily injection of PI3K/Akt signaling inhibitor wortmannin(15μg·kg-1·d-1)during 28-d hindlimb suspension(HS).Ex vivo muscle functional testing,histological and immunohistochemical analysis were performed to determine the changes of soleus muscle function,mean muscle fiber cross-sectional area(CSA)and fiber type distribution.Western blot and real-time PCR analysis were also performed to evaluate the protein or mRNA expression of the markers involved in PI3K/Akt signaling pathway.RESULTS After 28-d HS,soleus muscle underwent profound muscle atrophy(-52.7% muscle mass vs.pre-HS baseline).The high dose ICT treatment significantly attenuated the decreases in soleus muscle mass(+22.6% vs.HS),muscle fiber CSA(+52.8% vs.HS),as well as the muscle functional testing parameters during the unloading.Molecularly,the high dose ICT treatment significantly attenuated the decreases in protein synthesis markers at protein levels(phosphorylation of Akt and its downstream proteins)during the unloading,whereas the increases in protein degradation markers at mRNA(atrogin-1and MuRF-1)and protein(nuclear FOXO1 and FOXO3a)levels during the unloading were significantly attenuated by the high dose ICT treatment.The low dose ICT treatment moderately attenuated the above changes induced by the unloading.Mechanistically,Wortmannin could abolish the above effects of ICT.CONCLUSION ICT requires participation of PI3K/Akt signaling to counteract skeletal muscle atrophy following mechanical unloading in a dose-dependent manner.展开更多
目的探究采用MRI定量分析慢性踝关节不稳(chronic ankle instability,CAI)患者小腿肌肉横截面积(cross-sectional area,CSA)和质子密度脂肪分数(proton density fat fraction,PDFF)的改变及其相关影响因素。材料与方法前瞻性招募50名CA...目的探究采用MRI定量分析慢性踝关节不稳(chronic ankle instability,CAI)患者小腿肌肉横截面积(cross-sectional area,CSA)和质子密度脂肪分数(proton density fat fraction,PDFF)的改变及其相关影响因素。材料与方法前瞻性招募50名CAI患者和32名健康志愿者,收集他们的临床资料并行小腿肌肉MRI扫描。在轴位T1加权快速扰相梯度回波序列上勾画小腿各肌肉CSA,通过最小二乘法估计和不对称回波迭代分解水和脂肪成像获取相应肌肉PDFF。分析CAI患者小腿肌肉CSA和PDFF与健康对照组的差异并分析其与扭伤次数、中断活动时间、扭伤时间、足踝能力测量-日常生活评分(Foot and Ankle Ability Measure-Activities of Daily Living,FAAM-ADL)和足踝能力测量-运动评分(FAAM-SPORTS)的相关性。结果CAI患者患侧小腿腓肠肌内外侧头、比目鱼肌、胫骨前肌、胫骨后肌和腓骨长肌CSA较健康对照组减小,且PDFF增加,差异均有统计学意义(P均<0.05)。趾长伸肌和踇长屈肌CSA较健康对照组减小,差异无统计学意义(P=0.307、0.320);但两者PDFF较健康对照组增加,且差异有统计学意义(P=0.047、0.029)。相关性分析显示CSA减少与扭伤次数呈强正相关(r=0.785,P<0.001),与FAAM-ADL(r=-0.754,P<0.001)、FAAM-SPORTS(r=-0.766,P<0.001)呈强负相关,与中断活动时间呈中度正相关(r=0.642,P<0.001)。PDFF增加与扭伤次数呈强正相关(r=0.757,P<0.001)与FAAM-SPORTS呈强负相关(r=-0.740,P<0.001),与中断活动时间呈中度正相关(r=0.600,P<0.001),与FAAM-ADL呈中度负相关(r=-0.681,P<0.001)。结论MRI能定量评估CAI患者小腿肌肉CSA和PDFF改变,且与扭伤次数、FAAM-ADL、FAAM-SPORTS和中断活动时间有关。展开更多
目的探讨电针延缓大鼠失神经骨骼肌萎缩的可能机制。方法 21只雄性Sprague-Dawley大鼠随机分为假手术组(n=7)、模型组(n=7)和电针组(n=7)。后两组切断右侧坐骨神经制备大鼠失神经骨骼肌萎缩模型。造模后1 d,电针组电针术侧足三里和环跳...目的探讨电针延缓大鼠失神经骨骼肌萎缩的可能机制。方法 21只雄性Sprague-Dawley大鼠随机分为假手术组(n=7)、模型组(n=7)和电针组(n=7)。后两组切断右侧坐骨神经制备大鼠失神经骨骼肌萎缩模型。造模后1 d,电针组电针术侧足三里和环跳穴。干预8周后取双侧腓肠肌,称重,计算各组大鼠腓肠肌湿重比;HE染色测量肌纤维截面积和直径;逆转录实时定量聚合酶链反应检测大鼠术侧腓肠肌中自噬相关基因ULK1、Atg13、Beclin1、Atg14、Atg7、Atg12、Atg5和Atg16L1 m RNA表达。结果与假手术组相比,模型组和电针组术侧腓肠肌湿重比、肌纤维截面积及直径显著下降(P<0.001),但电针组高于模型组(P<0.05)。与假手术组相比,模型组术侧腓肠肌中ULK1、Atg13、Beclin1、Atg14、Atg7、Atg12、Atg5和Atg16L1 m RNA表达量显著升高(P<0.001);与模型组相比,电针组以上m RNA表达量均下降(P<0.05)。结论电针干预可能通过调控自噬相关基因的表达,抑制自噬过度激活,从而维持骨骼肌细胞稳态,延缓失神经骨骼肌萎缩。展开更多
基金The project supported by National Natural Science Foundation of China(81201406)Direct Grant for Research,The Chinese University of Hong Kong(4054138)
文摘OBJECTIVE Skeletal muscle undergoes rapid and profound atrophy in response to decreased mechanical loading,e.g.,limb immobilization and bed rest.Phosphatidylinositol 3 kinase(PI3K)/Akt signaling pathway is critical for regulating the balance between protein synthesis and degradation during disuse/inactivity-induced muscle atrophy.The present study aimed to investigate whether natural product Icaritin(ICT)required PI3K/Akt signaling to exert counteractive effect on skeletal muscle atrophy following mechanical unloading.METHODS Two oral dosages of ICT(80and 120mg·kg-1·d-1)were administrated daily to adult male rats with or without daily injection of PI3K/Akt signaling inhibitor wortmannin(15μg·kg-1·d-1)during 28-d hindlimb suspension(HS).Ex vivo muscle functional testing,histological and immunohistochemical analysis were performed to determine the changes of soleus muscle function,mean muscle fiber cross-sectional area(CSA)and fiber type distribution.Western blot and real-time PCR analysis were also performed to evaluate the protein or mRNA expression of the markers involved in PI3K/Akt signaling pathway.RESULTS After 28-d HS,soleus muscle underwent profound muscle atrophy(-52.7% muscle mass vs.pre-HS baseline).The high dose ICT treatment significantly attenuated the decreases in soleus muscle mass(+22.6% vs.HS),muscle fiber CSA(+52.8% vs.HS),as well as the muscle functional testing parameters during the unloading.Molecularly,the high dose ICT treatment significantly attenuated the decreases in protein synthesis markers at protein levels(phosphorylation of Akt and its downstream proteins)during the unloading,whereas the increases in protein degradation markers at mRNA(atrogin-1and MuRF-1)and protein(nuclear FOXO1 and FOXO3a)levels during the unloading were significantly attenuated by the high dose ICT treatment.The low dose ICT treatment moderately attenuated the above changes induced by the unloading.Mechanistically,Wortmannin could abolish the above effects of ICT.CONCLUSION ICT requires participation of PI3K/Akt signaling to counteract skeletal muscle atrophy following mechanical unloading in a dose-dependent manner.
文摘目的探究采用MRI定量分析慢性踝关节不稳(chronic ankle instability,CAI)患者小腿肌肉横截面积(cross-sectional area,CSA)和质子密度脂肪分数(proton density fat fraction,PDFF)的改变及其相关影响因素。材料与方法前瞻性招募50名CAI患者和32名健康志愿者,收集他们的临床资料并行小腿肌肉MRI扫描。在轴位T1加权快速扰相梯度回波序列上勾画小腿各肌肉CSA,通过最小二乘法估计和不对称回波迭代分解水和脂肪成像获取相应肌肉PDFF。分析CAI患者小腿肌肉CSA和PDFF与健康对照组的差异并分析其与扭伤次数、中断活动时间、扭伤时间、足踝能力测量-日常生活评分(Foot and Ankle Ability Measure-Activities of Daily Living,FAAM-ADL)和足踝能力测量-运动评分(FAAM-SPORTS)的相关性。结果CAI患者患侧小腿腓肠肌内外侧头、比目鱼肌、胫骨前肌、胫骨后肌和腓骨长肌CSA较健康对照组减小,且PDFF增加,差异均有统计学意义(P均<0.05)。趾长伸肌和踇长屈肌CSA较健康对照组减小,差异无统计学意义(P=0.307、0.320);但两者PDFF较健康对照组增加,且差异有统计学意义(P=0.047、0.029)。相关性分析显示CSA减少与扭伤次数呈强正相关(r=0.785,P<0.001),与FAAM-ADL(r=-0.754,P<0.001)、FAAM-SPORTS(r=-0.766,P<0.001)呈强负相关,与中断活动时间呈中度正相关(r=0.642,P<0.001)。PDFF增加与扭伤次数呈强正相关(r=0.757,P<0.001)与FAAM-SPORTS呈强负相关(r=-0.740,P<0.001),与中断活动时间呈中度正相关(r=0.600,P<0.001),与FAAM-ADL呈中度负相关(r=-0.681,P<0.001)。结论MRI能定量评估CAI患者小腿肌肉CSA和PDFF改变,且与扭伤次数、FAAM-ADL、FAAM-SPORTS和中断活动时间有关。
文摘目的探讨电针延缓大鼠失神经骨骼肌萎缩的可能机制。方法 21只雄性Sprague-Dawley大鼠随机分为假手术组(n=7)、模型组(n=7)和电针组(n=7)。后两组切断右侧坐骨神经制备大鼠失神经骨骼肌萎缩模型。造模后1 d,电针组电针术侧足三里和环跳穴。干预8周后取双侧腓肠肌,称重,计算各组大鼠腓肠肌湿重比;HE染色测量肌纤维截面积和直径;逆转录实时定量聚合酶链反应检测大鼠术侧腓肠肌中自噬相关基因ULK1、Atg13、Beclin1、Atg14、Atg7、Atg12、Atg5和Atg16L1 m RNA表达。结果与假手术组相比,模型组和电针组术侧腓肠肌湿重比、肌纤维截面积及直径显著下降(P<0.001),但电针组高于模型组(P<0.05)。与假手术组相比,模型组术侧腓肠肌中ULK1、Atg13、Beclin1、Atg14、Atg7、Atg12、Atg5和Atg16L1 m RNA表达量显著升高(P<0.001);与模型组相比,电针组以上m RNA表达量均下降(P<0.05)。结论电针干预可能通过调控自噬相关基因的表达,抑制自噬过度激活,从而维持骨骼肌细胞稳态,延缓失神经骨骼肌萎缩。
