The regulatory mechanism of protein conversion in skeletal muscle atrophy induced by hypoxia in rats

  OBJECTIVE: To compare the differences in the expression of genes related to protein synthesis and decomposition in rat skeletal muscle under hypoxic exposure and paired hypoxic feeding intervention (semi-starved state) under normoxia and to explore the possible mechanism of hypoxia exposure-induced skeletal muscle atrophy.

  Methods: SD rats were divided into: ① normal oxygen diet group (group C); ② normal hypoxic diet group (group H), with an oxygen concentration of 12.4%; ③ normoxia paired diet group (group P), the amount of feed It is the food intake of the H group the day before. After 4 weeks of intervention, the body composition of the rats was measured, the soleus muscle (SOL) and extensor digitorum longus (EDL) were taken, and the wet weight was measured. The muscle fiber morphology was observed by HE staining, and the muscle fiber cross-sectional area was calculated ( FCSA); WB tests the protein content of HIF1α, Akt, p-Akt and skeletal muscle protein synthesis and decomposition related genes in skeletal muscle.

  Results: 1) The weight of rats in group H continued to decrease compared with group C, and there was no significant difference between group P and group C; the food intake of group H (same as group P) was significantly lower than that of group C at the initial stage of intervention, and there was no difference between the two groups in the later period; (2) After the intervention, the body mass and total muscle mass of rats in group H were significantly lower than those in groups C and P, and there was no difference between group P and group C; the wet weight of the two muscles in group H was significantly lower than that in group C; EDL in group H The FCSA of group H was significantly lower than that of group C and group P; (3) The content of HIF1α protein in EDL of group H was significantly higher than that of group C; the ratio of p-Akt/Akt in SOL of group H and P was significantly lower than that of group C; in group H EDL The protein content of mTOR, 4EBP1 was significantly lower than that of group C. The protein content of atrogin1, MuRF1, beclin1 and the ratio of LC3Ⅱ/I were significantly higher than those of group C. The protein content of MuRF1 in SOL of group H was significantly higher than that of group C and P. Conclusions caused by hypoxia The skeletal muscle atrophy is induced by hypoxia-specific factors, manifested as a decrease in the synthesis and decomposition of skeletal muscle protein, which is dominated by fast muscle, rather than a decrease in food intake under hypoxia.