Frequent Tetanic Exercise Through Electrical Muscle Stimulation May Reduce Immobilization-Induced Muscle Fibrosis by Suppressing Myonuclear Apoptosis.

Abstract

Introduction/aims: Immobilization-induced fibrosis is the primary pathogenesis of muscle contracture, and its trigger is myonuclear apoptosis. Tetanic exercise through electrical muscle stimulation may be able to mitigate myonuclear apoptosis; this could be an intervention strategy for Immobilization-induced fibrosis. In the present study, this was tested using rat skeletal muscles.

Methods: Rats were divided into the control, immobilization, low-contraction frequency (LCF), and high-contraction frequency (HCF) groups. The soleus muscles were used as specimens.

Results: The number of TUNEL-positive myonuclei was 0.36 ± 0.11, 4.66 ± 0.90, 4.25 ± 0.99, and 1.90 ± 0.46 in the control, immobilization, LCF, and HCF groups, respectively. The HCF group was lower than the immobilization and LCF groups (all p < 0.001). The number of myonuclei and cross-sectional area (CSA) in the HCF group was higher than in the immobilization and LCF groups (all p < 0.001). The number of macrophages, mRNA expression of IL-1β, TGF-β1, and α-SMA, and hydroxyproline contents in the HCF group was lower than in the immobilization and LCF groups (all p < 0.001). There were moderate to strong negative correlations between the number of TUNEL-positive myonuclei and the number of myonuclei and between the CSA and the number of macrophages. Moderate to strong positive correlations were found between the number of myonuclei and the CSA, the number of macrophages and IL-1β, IL-1β and TGF-β1, TGF-β1 and α-SMA, and α-SMA and hydroxyproline contents.

Discussion: Frequent tetanic exercise might mitigate macrophage accumulation caused by myonuclear apoptosis and suppress immobilization-induced muscle fibrosis due to fibrosis-associated molecule overexpression.