Mackey Abigail L, Rasmussen Lotte K, Kadi Fawzi, Schjerling Peter, Helmark Ida C, Ponsot Elodie, Aagaard Per, Durigan João Luiz Q, Kjaer Michael
Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery M, Bispebjerg Hospital, Copenhagen, Denmark; Department of Biomedical Sciences, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery M, Bispebjerg Hospital, Copenhagen, Denmark;
FASEB J. 2016 Jun;30(6):2266-81. doi: 10.1096/fj.201500198R. Epub 2016 Mar 2.
With this study we investigated the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in human skeletal muscle regeneration. Young men ingested NSAID [1200 mg/d ibuprofen (IBU)] or placebo (PLA) daily for 2 wk before and 4 wk after an electrical stimulation-induced injury to the leg extensor muscles of one leg. Muscle biopsies were collected from the vastus lateralis muscles before and after stimulation (2.5 h and 2, 7, and 30 d) and were assessed for satellite cells and regeneration by immunohistochemistry and real-time RT-PCR, and we also measured telomere length. After injury, and compared with PLA, IBU was found to augment the proportion of ActiveNotch1(+) satellite cells at 2 d [IBU, 29 ± 3% vs. PLA, 19 ± 2% (means ± sem)], satellite cell content at 7 d [IBU, 0.16 ± 0.01 vs. PLA, 0.12 ± 0.01 (Pax7(+) cells/fiber)], and to expedite muscle repair at 30 d. The PLA group displayed a greater proportion of embryonic myosin(+) fibers and a residual ∼2-fold increase in mRNA levels of matrix proteins (all P < 0.05). Endomysial collagen was also elevated with PLA at 30 d. Minimum telomere length shortening was not observed. In conclusion, ingestion of NSAID has a potentiating effect on Notch activation of satellite cells and muscle remodeling during large-scale regeneration of injured human skeletal muscle.-Mackey, A. L., Rasmussen, L. K., Kadi, F., Schjerling, P., Helmark, I. C., Ponsot, E., Aagaard, P., Durigan, J. L. Q., Kjaer, M. Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication.
在本研究中,我们调查了非甾体抗炎药(NSAIDs)在人体骨骼肌再生中的作用。年轻男性在一条腿的伸肌接受电刺激诱导损伤前2周和损伤后4周,每天摄入NSAID[1200 mg/d布洛芬(IBU)]或安慰剂(PLA)。在刺激前后(2.5小时以及2、7和30天)从股外侧肌采集肌肉活检样本,通过免疫组织化学和实时逆转录聚合酶链反应评估卫星细胞和再生情况,我们还测量了端粒长度。损伤后,与PLA组相比,发现IBU在第2天可增加活化Notch1(+)卫星细胞的比例[IBU组为29±3%,PLA组为19±2%(均值±标准误)],在第7天增加卫星细胞含量[IBU组为0.16±0.01,PLA组为0.12±0.01(Pax7(+)细胞/纤维)],并在第30天加快肌肉修复。PLA组显示出更高比例的胚胎型肌球蛋白(+)纤维,基质蛋白的mRNA水平残留约2倍的增加(所有P<0.05)。在第30天,PLA组的肌内膜胶原蛋白也有所升高。未观察到端粒长度缩短至最小值。总之,摄入NSAID对损伤的人体骨骼肌大规模再生过程中卫星细胞的Notch激活和肌肉重塑具有增强作用。-麦基,A.L.,拉斯穆森,L.K.,卡迪,F.,施耶林,P.,赫尔马克,I.C.,庞索,E.,阿加德,P.,杜里甘,J.L.Q.,克亚尔,M.摄入非甾体抗炎药物可加快卫星细胞的激活和人体骨骼肌的再生。