Abstract:

BACKGROUND: Nuclear factor κB (NF-κB)/ muscle RING finger protein1 (MuRF1) pathway is one of the most important molecular mechanisms in skeletal muscle atrophy. Inhibiting of NF-κB / MuRF1 pathway improves denervated skeletal muscle strength, maintains muscle mass, and promotes regeneration.
OBJECTIVE: To explore the expression of NF-κB and MuRF1 in denervated skeletal muscle atrophy in rats and the effect of losartan on NF-κB / MuRF1 pathway.
METHODS: Wistar rats were randomly divided into 3 groups. The denervated and Losartan groups were subjected to establishment of denervated gastrocnemius models followed by normal saline perfusion or losartan 10 mg/kg per day. The control group was not treated. After 2, 14 and 28 days, levels of NF-κB and MuRF1 mRNA and protein in the gastrocnemius were detected respectively by RT-PCR and Western bloting. The ratio of muscle wet weight was also analyzed for comparison.
RESULTS AND CONCLUSION: Expressions of NF-κB and MuRF1 mRNA and protein in denervated skeletal muscle were up-regulated at 2, 14, and 28 days following denervation (P < 0.05). Moreover, NF-κB expression of positively correlated with MuRF1 expression (P < 0.05). At 14 and 28 days after denervation, the losartan group had a greater ratio of muscle wet weight compared with denervated group (P < 0.05). The expression of NF-κB and MuRF1 mRNA and protein in losartan group remarkably reduced compared with denervated group (P < 0.05) at each time point. At the early stage of denervated skeletal muscle atrophy， expression of NF-κB and MuRF1 was up-regulated， suggesting the presence of NF-κB / MuRF1 pathway. Results show that losartan can decrease denervated skeletal muscle atrophy through NF-κB/MuRF1 pathway.