Denervated Skeletal Muscle Atrophy And Experimental Study On Losartan Decreasing Muscle Atrophy Through NF-κB/MuRF1 Pathway

OBJECTIVE:To explore the role of nuclear factor ofκB(NF-κB) and muscle RING finger protein1(MuRF1) in denervated skeletal muscle atrophy in rats and the effect of losartan on it. NF-κB/MuRF1 pathway is one of the most important molecular mechanism in skeletal muscle atrophy. Inhibiting of NF-κB/MuRF1 pathway improves denervated skeletal muscle strength,maintains mass,and promotes regeneration.METHODS:Forty two Wistar rats were randomly divided into 3 groups:Denervated group(n=18). Losartan group (n=18). control group (n=6).The rats were not treated in control group,and were made denervated gastrocnemius models in denervated group and losartan group. In losartan group, the rats were treated with losartan 10mg/kg·d by gavage and with normal saline in denervated group. After 2 day,14day and 28day,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:Expressions of NF-κB and MuRFl mRNA and protein in denervated skeletal muscle were up-regulated at 2,14,28 days in the early stage of denervation(P<0.05).Moreover, The expressions of NF-κB positively correlated with the expressions of MuRF1(P＜0.05). At 14,28 days after denernation, The losartan group(B) had a higher ratio of muscle wet weight than denervated group(A)(P<0.05). At2,14,28 days after denernation, The expression of NF-kB and MuRF1 in losartan group remarkably reduced comparing with the denervated group (P＜0.05).CONCLUTION:At the early stage of denervated skeletal muscle atrophy in Wistar rats, expressions of NF-κB and MuRF1 are up-regulated, and proved NF-κ/MuRF1 pathway was exist. Losartan can decrease denervated skeletal muscle atrophy through NF-κB/MuRF1 pathway.