| 초록 |
Objectives : Cardiac hypertrophy and sarcopenia are common in dialysis patients and result in high probability for morbidity and mortality. Aktmammalian traget of rapamycin (mTOR) axis is related with cardiac hypertrophy and muscle atrophy. Myostatin, a member of TGF-β superfamily, is produced in the skeletal muscle to inhibit myocyte differentiation. Myostatin expression is increased in patients with heart failure and chronic kidney disease. The present study aimed to investigate whether omega-3 fatty acid (FA) and cholecalciferol affect on molecules associated with cardiac hypertrophy and sarcopenia in 5/6 nephrectomy (Nx) rats.
Methods : Male Sprague Dawley rats were divided into five groups and treated for 6 weeks: sham control (0.9% saline), 5/6 Nx control (0.9% saline), 5/6 Nx treated with vitamin D (cholecalciferol 3000 IU/kg/week by gastric gavage), 5/6 Nx treated with omega-3 FA (300 mg/kg/day by gastric gavage), 5/6 Nx treated with vitamin D and omega-3 FA. The expression of myostatin, myogenin, MyoD, Akt, phosphrylated(p) Akt, PI3K, p-PI3k, P38, p-P38 and mTOR were examined by western blot analysis.
Results : Serum blood urea nitrogen and creatinine were the lowest in 5/6 Nx group treated with omega-3 FA and vitamin D among other 5/6 Nx groups. Compared with sham control, 5/6 Nx control significantly up-regulated myostatin and down-regulated myogenin and MyoD in both cardiac and skeletal muscle. Increased expression of myostatin and decreased expression of myogenin and MyoD of cardiac and skeletal muscle were recovered by combined treatment with omega-3 FA and cholecalciferol. MyoD of skeletal muscle was dominantly regulated by cholecalciferol supplementation. Phosphorylated Akt and mTOR were up-regulated in the cardiac muscle but down-regulated in the skeletal muscle of 5/6 Nx control compared to sham control. Combined therapy of omega-3 FA and cholecalciferol decreased p-Akt and mTOR expression in cardiac muscle and increased p-Akt and mTOR expression in skeletal muscle of 5/6 Nx rats.
Conclusions : Combined therapy of omega-3 FA and cholecalciferol may be helpful for decreasing cardiac hypertrophy and sarcopenia by increasing myogenin and MyoD, decreasing myostatin and modulating Akt-mTOR axis in both cardiac and skeletal muscle of 5/6 Nx rats. |