Durigan João Luiz Quagliotti, Peviani Sabrina Messa, Delfino Gabriel Borges, de Souza José Rebeca Jomori, Parra Talita, Salvini Tania Fátima
From the Physical Therapy Division, Faculty of Ceilândia, University of Brasília, Distrito Federal, Brazil (JLQD); and Department of Physical Therapy, Federal University of São Carlos, São Paulo, Brazil (SMP, GBD, RJdSJ, TP, TFS).
Am J Phys Med Rehabil. 2014 Nov;93(11):948-61. doi: 10.1097/PHM.0000000000000110.
The aim of this study was to assess the effect of neuromuscular electrical stimulation (NMES) on the extracellular matrix remodeling of the quadriceps muscle after anterior cruciate ligament (ACL) transection in rats. The hypothesis of this study was that ACL transection would induce maladaptive modifications in the extracellular matrix through the increase in connective tissue (CT) accumulation and net degradation of type IV collagen of the quadriceps muscle. In addition, clinical-like NMES, applied to the quadriceps muscle immediately after the ACL transection, would reduce the accumulation of the CT content and net degradation of type IV collagen.
Wistar male rats were randomized into five different groups: ACL (surgery and ACL transection), Sham (surgery without ACL transection), ACLES (surgery, ACL transection, and NMES), ShamES (surgery without ACL transection, but NMES), and Control (intact animals). The vastus medialis, rectus femoris, and vastus lateralis muscles of the quadriceps were harvested 1, 2, 3, 7, and 15 days after surgery. Matrix metalloproteinase-2 (MMP-2) (messenger RNA [mRNA] levels and activity), collagen IV (mRNA and protein levels), and CT density were assessed.
The ACL transection increased the CT content and MMP-2 mRNA levels and decreased collagen IV mRNA and protein levels. NMES minimized the CT density in all muscles and reduced the MMP-2 mRNA levels mainly in the vastus lateralis muscle at 7 days. Moreover, type IV collagen mRNA levels were increased in all muscles at 7 days, as was the protein level only at 15 days, in the NMES groups.
This study showed that ACL transection increases CT content and MMP-2 mRNA levels and induces rapid changes in basement membranes, causing net degradation of type IV collagen during the first 2 wks after ACL injury. Furthermore, clinical-like NMES minimized the accumulation of CT density, regulated the MMP-2 mRNA levels, and increased both type IV collagen mRNA and protein levels.
本研究旨在评估神经肌肉电刺激（NMES）对大鼠前交叉韧带（ACL）横断后股四头肌细胞外基质重塑的影响。本研究的假设是，ACL横断会通过股四头肌结缔组织（CT）积累增加和IV型胶原净降解，诱导细胞外基质的适应性不良改变。此外，在ACL横断后立即应用类似临床的NMES，会减少CT含量的积累和IV型胶原的净降解。
将雄性Wistar大鼠随机分为五个不同组：ACL组（手术及ACL横断）、假手术组（手术但未进行ACL横断）、ACLES组（手术、ACL横断及NMES）、ShamES组（手术未进行ACL横断，但给予NMES）和对照组（完整动物）。术后1、2、3、7和15天采集股四头肌的股内侧肌、股直肌和股外侧肌。评估基质金属蛋白酶-2（MMP-2）（信使核糖核酸[mRNA]水平和活性）、IV型胶原（mRNA和蛋白质水平）以及CT密度。
ACL横断增加了CT含量和MMP-2 mRNA水平，降低了IV型胶原mRNA和蛋白质水平。NMES使所有肌肉中的CT密度最小化，并主要在术后7天时降低了股外侧肌中的MMP-2 mRNA水平。此外，在NMES组中，术后7天时所有肌肉中的IV型胶原mRNA水平均升高，但仅在术后15天时蛋白质水平升高。
本研究表明，ACL横断会增加CT含量和MMP-2 mRNA水平，并在前2周内导致基底膜快速变化，引起IV型胶原的净降解。此外，类似临床的NMES使CT密度的积累最小化，调节了MMP-2 mRNA水平，并增加了IV型胶原mRNA和蛋白质水平。
