Therapeutic effect of passive mobilization exercise on improvement of muscle regeneration and prevention of fibrosis after laceration injury of rat

Abstract

OBJECTIVE: To evaluate the muscle healing effect of passive mobilization exercises after a laceration injury. DESIGN: Randomized‐controlled trial. SETTING: Basic science laboratory. ANIMALS: Male Sprague–Dawley rats (N=36), age ranging from 8 to 10 weeks and weight ranging from 300 to 400 g. INTERVENTION: The bilateral gastrocnemius muscles were lacerated. The left‐leg muscles were used as the study groups and the right side was used as the control (lacerated muscles without any treatment, n=8). In the exercise group (n=24), passive mobilization exercise (15 min/day) was performed for 5 days starting from different time points (2, 7, and 14 days postlaceration). The decorin group (n=8) was injected with decorin (50 μg at 14 days postlaceration), which is a well‐known antifibrotic agent. Four animals were used as the normal controls, in which only the muscle strength was evaluated. All the animals were killed 4 weeks after the laceration. MAIN OUTCOME MEASURES: The histologic characterization of muscle regeneration (hematoxylin and eosin staining, number and diameter of the centronucleated, regenerating myofibers), muscle fibrosis (vimentin‐positive area, Masson modified trichrome staining positive area), and muscle strength (analysis of fast twitch strength). RESULTS: The level of fibrosis was more than 50% lower in the exercise and decorin groups than in the control (P<0.05). The decorin group showed the highest number of regenerated, new myofibers, and the highest muscle strength. All of the exercise groups, regardless of the starting time of exercise, also showed significant improvement in regeneration and strength. However, the exercise group starting 14 days after the laceration showed the best results. CONCLUSIONS: Stretching exercises after a muscle laceration injury has a strong antifibrotic effect, as much as a well‐known antifibrotic agent, decorin. According to the results, the best time to begin stretching exercises is 14 days after laceration for antifibrosis and muscle regeneration.

Recovery of skeletal muscle mass after extensive injury: positive effects of increased contractile activity

“…The full recovery of muscle weight only 21 days after injury in Act rats appeared then as a striking result, all the more noteworthy as morphological data clearly showed that this was achieved by the development of myofibers, with less fibrosis development than in Reg muscles of Sed rats. These results strengthen previous observations that suggested that physical activity ensured to limit the appearance of connective tissue in Reg muscles (23).…”

Curto período de imobilização provoca alterações morfométricas e mecânicas no músculo de rato

“…Not only does the contractile activity decrease in the immobilized muscle, but there is also a mechanical load decrease. This also affects the proliferation of this tissue, once it regulates the production of growth factors and collagen synthesis 22 . In this sense, fibroblasts, which are subject to active and passive muscular tension, have their metabolism altered with the decreases of tension caused by immobilization, which incurs in area density increases of the intramuscular connective tissue.…”

Trends in Mesenchymal Stem Cells' Applications for Skeletal Muscle Repair and Regeneration

“…This particular growth factor is stimulatory to collagen and ECM deposition that can be detrimental to the skeletal muscle regeneration process, contributing to exacerbated fibrosis and loss of contractile properties [32]. When TGF-β1 activity is inhibited by the action of decorin, regeneration indexes significantly improve and fibrosis development decreases by 50% in laceration injuries [133], conveying toward in vitro observations [132]. TGF-β1 acts on myoblasts, leading to the overexpression of fibrosis-related proteins and the down-regulation of myogenic proteins (desmin, MyoD, and myogenin).…”