Changes of Apoptosis Related Factors in Atrophic Rat Skeletal Muscles after Denervation and Disuse

ABSTRACT

OBJECTIVE: To investigate the changes of apoptosis related factors after denervation and disuse in skeletal muscles and to find out the role of apoptosis in atrophic process. METHOD: 30 male Sprague-Dawley rats, 8 weeks of age were treated with three different atrophy models (10 rats in each group); hind-limbs suspension (HS) as a disuse model, complete denervation by sciatic nerve transsection (CD) and partial denervation by sciatic nerve crushing (PD). At 2 weeks and 4 weeks after each experiment, both gastrocnemius were dissected and their weights were measured. Western blotting for BAX and Bcl-2 and TUNEL assay were used to assess the changes of apoptosis related factors in muscle cell. RESULTS: The muscle weight of PD and CD group decreased 38.6%, 65.6%, respectively, of intact side at 4 weeks after injuries. The loss of muscle weight in HS group was smaller than that of denervated muscles. CD group showed high expression of BAX (3.45+/-0.32-->2.87+/-0.48) and Bcl-2 (3.63+/-0.40-->3.33+/-0.50) at 2 and 4 weeks after denervation, but in PD group, BAX at 2 weeks significantly decreased at 4 weeks (3.40+/-0.55-->2.13+/-0.25). In HS group, their expressions were slightly increased only immediate after 14 days suspension (BAX 1.30+/-0.38 and Bcl-2 1.29+/-0.28). CD group showed higher number of positive nuclei (27.6+/-8.8%) than PD group (10.4+/-5.3%) and HS group (4.4+/-1.6%) in TUNEL assay. CONCLUSION: Unlike temporary increase of apoptosis related factors in disuse, increase of these factors are remarkable and persisted after denervation. Muscle apoptosis may be the major cause of muscle atrophy during degeneration process.