Table_2_Knee Extensors Muscle Plasticity Over a 5-Years Rehabilitation Process After Open Knee Surgery.docx

We investigated molecular and cellular parameters which set metabolic and mechanical functioning of knee extensor muscles in the operated and contralateral control leg of 9 patients with a chronically insufficient anterior cruciate ligament (ACL; 26.6 ± 8.3 years, 8 males, 1 female) after open reconstructive surgery (week 0), after ambulant physiotherapy under cast immobilization (week 9), succeeding rehabilitation training (up to week 26), and subsequent voluntary physical activity (week 260). Clinical indices of knee function in the operated leg were improved at 52 weeks and remained at a comparable level at week 260. CSA of the quadriceps (-18%), MCSA of muscle fibers (-24%), and capillary-to-fiber ratio (-24%) in m. vastus lateralis from the ACL insufficient leg were lower at week 0 than reference values in the contralateral leg at week 260. Slow type fiber percentage (-35%) and mitochondrial volume density (-39%) were reduced in m. vastus lateralis from the operated leg at weeks 9 and 26. Composition alterations in the operated leg exceeded those in the contralateral leg and, with the exception of the volume density of subsarcolemmal mitochondria, returned to the reference levels at week 260. Leg-specific deterioration of metabolic characteristics in the vasti from the operated leg was reflected by the down-regulation of mitochondrial respiration complex I-III markers (-41–57%) at week 9. After rehabilitation training at week 26, the specific Y397 phosphorylation of focal adhesion kinase (FAK), which is a proxy for mechano-regulation, was elevated by 71% in the operated leg but not in the contralateral leg, which had performed strengthening type exercise during ambulant physiotherapy. Total FAK protein and Y397 phosphorylation levels were lowered in both legs at week 26 resulting in positive correlations with mitochondrial volume densities and mitochondrial protein levels. The findings emphasize that a loss of mechanical and metabolic characteristics in knee extensor muscle remains detectable years after untreated ACL rupture, which may be aggravated in the post-operative phase by the deterioration of slow-oxidative characteristics after reconstruction due to insufficient load-bearing muscle activity. The reestablishment of muscle composition subsequent to years of voluntary physical activity reinforces that slow-to-fast fiber transformation is reversible in humans.

本研究针对9名慢性前交叉韧带（ACL）不全（平均年龄26.6±8.3岁，男性8名，女性1名）患者在开放性重建手术后（第0周），在石膏固定下的步行物理治疗之后（第9周），随后进行康复训练（至第26周），以及随后的自愿体力活动（第260周）期间，对其膝关节伸肌的分子和细胞参数进行了探讨，这些参数影响了膝关节伸肌的代谢和机械功能。术后52周，手术腿的膝关节功能临床指标得到改善，并在第260周保持与对侧腿相当的水平。ACL不全侧股外侧肌的肌肉横截面积（CSA）（-18%）、肌纤维最大横截面积（MCSA）（-24%）和毛细血管与肌纤维比率（-24%）在第0周低于对侧腿在第260周的参考值。在第9周和第26周，手术腿股外侧肌的慢肌纤维百分比（-35%）和线粒体体积密度（-39%）降低。手术腿的组成变化超过了对侧腿的变化，除了肌膜下线粒体体积密度外，均在第260周恢复至参考水平。手术腿外侧肌的代谢特性特异性下降在第9周表现为线粒体呼吸复合物I-III标记物的下调（-41–57%）。在第26周的康复训练后，机械调节的指标——焦磷酸化聚焦粘附激酶（FAK）的Y397磷酸化水平在手术腿中升高了71%，而对侧腿没有变化，因为在对侧腿的步行物理治疗期间进行了强化型运动。在第26周，两腿的FAK总蛋白和Y397磷酸化水平均降低，与线粒体体积密度和线粒体蛋白水平呈正相关。研究结果表明，未经治疗的ACL撕裂导致的膝关节伸肌机械和代谢特性的丧失在多年后仍然可检测到，这可能因重建后由于承重肌肉活动不足而导致的慢氧化特性的恶化而在术后阶段加剧。多年自愿体力活动后肌肉组成的重建强化了人类慢肌至快肌转变的可逆性。