| 초록 |
Myostatin is produced and released by myocytes and inhibits muscle cell growth and differentiation. However, muscular myostatin expression is not clear in rat model of chronic kidney disease. We aimed to investigate whether omega-3 fatty acids(FA) regulate the expression of mediators of mitochondrial dysfunction in muscle of adenine-induced uremic rats. In addition, we tried to elucidate whether omega-3 FA effects on muscular myostatin expression in uremic rat model. Male Sprague-Dawley rats were fed diets containing 0.75% adenine and 2.5% protein for three weeks. Next, rats were randomly divided into two groups that were fed diets containing 2.5% protein and saline with cholecalciferol (3000 IU/kg/week) or omega-3 FA (300 mg/kg/day) with cholecalciferol supplemented by gastric gavage for two weeks: normal control (n=6), adenine control sacrificed at 3 weeks (n=5), adenine control sacrificed at 5 weeks (n=5), omega-3 FA group sacrificed at 5weeks (n=5). The muscular expression of myostatin, PGC-1α, SIRT1 and Nrf2 were examined by western blot analysis. Quantitative real-time polymerase chain reaction was used to determine the relative mitochondrial DNA content of muscle. Compared to normal, serum creatinine in adenine control was increased and improved in the omega-3 FA group. PGC-1α, SIRT1, and Nrf2 were down-regulated in the muscle of adenine control at 3 and 5 weeks. Down-regulated PGC-1α, SIRT1, and Nrf2 were recovered with omega-3 FA supplementation for 2 weeks. Compared to normal, muscular myostatin expression was continuously downregulated at 3 and 5 weeks and recovered with omega-3 FA supplementation for 2 weeks. Mitochondrial DNA content of muscle was decreased in the muscle of adenine control and improved with omega-3 FA supplementation. Even in the status of increased muscular myostatin expression by omega-3 FA, omega-3 FA is beneficial for mitochondrial dysfunction of muscle in uremic rats. |