| 초록 |
Objectives: Osteopenia, sarcopenia, and vascular calcification (VC) are commonly observed in chronic kidney disease (CKD) and often coexist. Omega-3 fatty acid (OMEGA3-FA) and menaquinone-7 (MK-7) reduced VC in previous studies. The present study evaluated the effect of OMEGA3-FA and MK-7 on osteopenia and sarcopenia in adenine and low protein diet induced uremic rat model.
Methods: Male Sprague Dawley rats were fed the diets containing 0.75% adenine and 2.5% protein for three weeks. After three weeks, thirty two rats were randomly divided into four groups, which were treated and fed the diets containing 2.5% protein for 4 weeks: an adenine control (0.9% saline), a group treated with OMEGA3-FA (300 mg/kg/day), a group treated with MK-7 (50 ug/kg/day), and a group treated with OMEGA3-FA and MK-7. For quantitative assessment of aortic calcification (AC), von Kossa stain was done. Osteoclast surface/bone surface ratio (OcS/BS) was analysed using H&E stain. Proteins associated with sarcopenia were examined using Western blot analysis.
Results: OcS/BS and AC area were significantly increased in adenine control group compared to normal control group. OcS/BS and AC were the least progressed in the combined treatment group compared to groups treated with either OMEGA3-FA or MK-7. The regular arrangement of muscle fiber was severely disrupted and inflammatory cell infiltration was more prominent in adenine control group. These findings were reduced after combination treatment with OMEGA3-FA and MK-7. Decreased expression of myostatin in the adenine control group was significantly restored by OMEGA3-FA and MK-7 combined treatment. Inflammatory cytokines and mTOR expression were restored by OMEGA3-FA. Fox01 and Fox03a were up-regulated in the adenine control and Fox01 was restored only by the combined treatment.
Conclusions: The combined treatment with OMEGA3-FA and MK-7 prevents osteopenia progression and partially improves sarcopenia related molecules in an adenine and low protein diet induced uremic and VC rat model.
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