부산대학교 도서관

Musculoskeletal disorders are one of the main causes of requirement for functional rehabilitation in the world. In sports, musculoskeletal system injuries represent between 10-55% of all sustained injuries. Because of its high incidence and impact on health, skeletal muscle regeneration process has been extensively studied and characterized. However, still new therapeutic strategies need to be studied in order to accelerate the muscle regeneration process and ameliorate muscle tissue after injury. Due to its high plasticity, skeletal muscle can adapt and respond to different stimuli in order to maintain the homeostasis and improve its functionality. It has been well stablished that intermittent hypobaric hypoxia (HHI) can improve muscle oxygen transport, delivery and utilization. However, hypobaric hypoxia always coexist with cold in the biosphere, opening the possibility to consider the combined use of the exposure to these two environmental factors as a tool to achieve beneficial physiological and muscular adaptations. Therefore, in the present thesis we studied the effects of HHI and intermittent cold exposure, separately and in combination, on the physiology of an animal model and more specifically on the processes of muscle regeneration. Sprague-Dawley adult-male rats were used as an experimental model. The animals were surgically injured in one of their gastrocnemius muscles and then randomly divided into different groups: 1) CTRL group: animals with passive recovery; 2) COLD group: animals exposed to intermittent cold (4°C); 3) HYPO group: animals submitted to HHI (simulated altitude of 4,500 m); 4) COHY group: animals exposed to intermittent cold and hypoxia simultaneously (4,500 m + 4°C). All animals were subjected to the different interventions for 4 h/day during 9 or 21 days. Moreover, two additional groups were included, the first one to corroborate morpho-functional symmetry between the right and left gastrocnemius muscles, and the second one to validate the protocol of injury induction. Our results showed the existence of morphological (fibre cross-sectional area and fibre proportion) and functional (force and resistance to fatigue) symmetry between the right and the left gastrocnemius muscles of the rats. The method used to induce a muscle injury was proved optimal, because it caused functional and structural disorders. The use of intermittent exposure protocols guaranteed normal growth and increased muscle mass in the animals, additionally inducing acclimatative responses such as increments in brown adipose tissue in the animals exposed to cold (COLD and COHY) and increments in blood oxygen transport capacity in animals exposed to hypoxia (HYPO and COHY). At the muscular level, the COLD group exhibited enhanced muscle capilarisation, through increments in VEGF and in the number of capillaries, whilst HYPO and COHY groups improved skeletal muscle vascularisation due to a reduction in fibre size, but without detecting an increased angiogenic process. Animals from COLD and COHY groups presented faster muscle regeneration, which was observed at the histological level after 9 days (reduction in the percentage of dMHC positive fibres and with central myonuclei) and at the functional level after 21 days. HYPO group showed a fully recovery from injury (both at the histological and functional levels) after 9 days. Furthermore, HHI can be postulated as an interesting anti-fibrotic, by reducing collagen I deposition at the site of injury. The increase in the pSer473Akt/total Akt ratio observed after 9 days of treatment in the COLD, HYPO and COHY groups, together with the increase in the pThr172AMPKα/total AMPKα ratio observed in the gastrocnemius muscles of HYPO groups, provide clues to the possible responsible mechanisms involved in the observed improvement of muscle regeneration.