Russo Thiago Luiz, Peviani Sabrina Messa, Durigan João Luiz Quagliotti, Salvini Tania Fátima
Department of Physical Therapy, Federal University of São Carlos, Rodovia Washington Luís, Km 235, CEP 13565-905, São Carlos, São Paulo, Brazil.
Muscle Nerve. 2008 May;37(5):593-600. doi: 10.1002/mus.20985.
Muscle-fiber atrophy occurs concomitantly with intramuscular connective tissue proliferation following denervation. These events contribute to the impairment of mechanical and functional properties of denervated muscles and compromise their recovery. Electrical stimulation (ES) is used in human rehabilitation to treat denervated muscles. However, the effects of this therapy on the intramuscular extracellular matrix (ECM) remain uncertain. Metalloproteinases (MMPs) are responsible by remodeling ECM in many neuromuscular disorders. This study evaluates the effect of ES on the activity of two important MMPs, MMP-2 and MMP-9, both involved in ECM remodeling of rat denervated muscles. Thirty-four Wistar rats (3 months old, 356 +/- 38.7 g) were divided into five groups: denervated (D); D+ES; sham denervation; normal (N); and N+ES. Twenty maximal muscle contractions were stimulated every 48 h using surface electrodes, as generally used in the rehabilitation of human denervated muscle. Both zymographic analysis and real-time polymerase chain reaction (PCR) of MMPs were used to evaluate muscle after denervation for 28 days. Both the D and D+ES groups showed increased MMP-2 activity compared with the N group (P < 0.05). Furthermore, only the D+ES had increased MMP-2 gene expression compared with the N group (P < 0.05). MMP-9 activity was not detected in any of the groups. The results of this study indicate that denervation increases MMP-2 activity, and ES regulates MMP-2 gene expression in rat denervated skeletal muscle. These findings clarify the effects of ES on the ECM of denervated muscle and may be helpful in designing new therapeutic strategies for rehabilitation in patients with denervation of muscle.
去神经支配后，肌纤维萎缩与肌内结缔组织增生同时发生。这些事件导致去神经肌肉的力学和功能特性受损，并影响其恢复。电刺激（ES）用于人类康复治疗去神经肌肉。然而，这种疗法对肌内细胞外基质（ECM）的影响仍不确定。金属蛋白酶（MMPs）在许多神经肌肉疾病中负责ECM重塑。本研究评估ES对两种重要MMPs（MMP-2和MMP-9）活性的影响，这两种酶都参与大鼠去神经肌肉的ECM重塑。34只Wistar大鼠（3个月大，356±38.7 g）分为五组：去神经支配组（D）；D+ES组；假去神经支配组；正常组（N）；和N+ES组。如人类去神经肌肉康复中常用的那样，每48小时使用表面电极刺激20次最大肌肉收缩。采用MMPs的酶谱分析和实时聚合酶链反应（PCR）评估去神经28天后的肌肉。与N组相比，D组和D+ES组的MMP-2活性均增加（P<0.05）。此外，与N组相比，只有D+ES组的MMP-2基因表达增加（P<0.05）。所有组均未检测到MMP-9活性。本研究结果表明，去神经支配增加MMP-2活性，ES调节大鼠去神经骨骼肌中MMP-2基因表达。这些发现阐明了ES对去神经肌肉ECM的影响，可能有助于设计针对肌肉去神经支配患者康复的新治疗策略。
