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Astragalus polysaccharides decrease muscle wasting through Akt/mTOR, ubiquitin proteasome and autophagy signalling in 5/6 nephrectomised rats

2016; Elsevier BV; Volume: 186; Linguagem: Inglês

10.1016/j.jep.2016.03.068

1872-7573

Lu Lu, Yanfeng Huang, Dexiu Chen, Ming Wang, Yucong Zou, Heng Wan, Lianbo Wei,

Adipose Tissue and Metabolism

Existing evidences suggest that Radix Astragali and its polysaccharides composition (APS) can improve muscle mass, but the mechanisms need more research.In this study, we aimed to examine the effects of APS on muscle wasting at molecular level in 5/6 nephrectomised rats.We performed 5/6 nephrectomy or sham operation in 160 6-week-old Sprague-Dawley rats, and feed animals with or without 2% APS for 155 days. After treatment, we compared the change of weight, muscle fibre, protein metabolism, pro-inflammatory factors (TNF-α, IL-15, CRP) and oxidative factors (MDA, SOD) among each group. In addition, we detected the Akt/mTOR, ubiquitin proteasome, autophagy signalling and AA transporters in vivo and in vitro.Data in vivo show 2% APS could alleviate weight loss and improve protein metabolism in nephrectomised rats. The levels of serum pro-inflammatory factors and oxidative factors were restored by APS treatment. In molecular levels, APS restored Akt/mTOR, MAFbx, MuRF1, Atg7, LC3B-II/LC3B-I and SLC38A2 which changed in nephrectomised rats. Data in vitro show the optimal dose of APS is 0.2mg/mL, and SLC38A2 siRNA attenuated the effects of 0.2mg/mL APS on atrophy and autophagy.Our results suggested APS could improve muscle wasting through Akt/mTOR, ubiquitin proteasome and autophagy signalling, and SLC38A2 may be one of potential targets.