Effect of chronic intermittent hypoxia exposure: differences on soleus muscle and musculi tibialis anterior

Abstract

Objective To compare the effects of chronic intermittent hypoxia exposure on different fiber types of muscle and investigate its possible mechanism. Methods Sixteen SD rats were randomly divided into normoxia control group (C group, placed in a normoxic chamber) and chronic intermittent hypoxia group (H group, placed in a hypoxic chamber with an oxygen concentration of 12.4%, 8 h per day, for 4 weeks). Their body mass was weighed during the intervention, and the grasping force and lean body mass were tested after the intervention. The wet masses of soleus muscle (SOL) and musculi tibialis anterior (TA), muscle fiber cross-sectional area (FCSA) were measured. The protein levels of puromycin (Puro) and ubiquitin (Ub) were detected with Western blotting. RNA sequencing was carried out for TA tissues to screen the differential genes between the 2 groups. And the biological process and pathways enriched by these differential genes were analyzed. Results ① During the intervention, the body mass of the C and H groups continued to increase, but it of the H group was always lower than that of the C group at each time point. The intervention also resulted in the decreases in the lean body mass and its percentage, grasping force and relative grasping force in the H group than the C group, but there were no statistical differences. ② The wet mass of TA was significantly lower in the H group than the C group (P < 0.05). In H group, both SOL and TA muscle fibers were damaged, and the FCSA of SOL was significantly lower than C group (P < 0.05). ③Puro and Ub in SOL tissues were obviously higher in the H group than the C group. The ratio of Puro/Ub was decreased significantly in SOL tissues (P < 0.05), but increased significantly in TA tissues (P < 0.01). ④ There were 665 differential genes found in SOL tissues and 228 differential genes in TA tissues between the 2 groups. Among them, 58 differential genes were up-regulated and 35 were down-regulated in both muscles. Those up-regulated differential genes in SOL tissues were mainly enriched in inflammatory response and protein synthesis and involved in TNF and Jak/STAT signaling pathways. The up-regulated differential genes in TA tissues were mainly enriched in antioxidant and glucose metabolism and glucocorticoid and involved in PPAR signaling pathway and glutathione metabolism. The down-regulated genes were concentrated in oxidative stress and transformation between fast- and slow-twitch muscles. Conclusion Chronic intermittent hypoxia could promote SOL atrophy by enhancing inflammatory response, and TA may resist hypoxia-induced muscle atrophy by improving antioxidant capacity.

Keywords

• chronic intermittent hypoxic exposure
• skeletal muscle
• muscle atrophy
• slow-twitch fibers
• fast-twitch fibers