Effects Of Hypoxia And Exercise On VEGF And BFGF Expression And Their Functions In Rats' Gastrocnemius Muscles

Objective: Investigation of hypoxia training becomes one of the fastest-progress research areas all around the world in these years, but there are lots of unknown things and arguement in its biologic mechanism and application. Capillary neogenesis is one of the main reflections of skeletal muscle's adaptation to hypoxia and exercise, because exercise induced muscle damage(EIMD) will occur when skeletal muscle undertakes unaccommodated exercise, which reparation progress may be accompanied with capillary neogenesis possibly through many cytokines. Vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF) are two of these cytokines which play important roles. However, the investigation of VEGF and bFGF is still the primary study process in the sports medicine field. Therefore, the present study was aimed to investigate the effects of hypoxia and/or exercise on the expression and time course of VEGF and bFGF in the rats' gastrocnemius, and the effects of VEGF and bFGF on the capillary neogenesis and reparation of EIMD by histological, molecular biological and immunohistochemical technology.Methods: Male SD rats were used to establish the acute exercise muscle injury models and then applied to either acute or short-term exercise training with different intensity of pure hypoxia, normoxia as a simulation of "living high-training low". At the different time points, many parameters are measured, respectively including the serum creatine kinase and lactate dehydrogenase (automatic biochemistry analysis instrument), the expression of VEGF (Western blot,ELISA) or bFGF (immunohistochemistry), the capillary density (CD, CD34 immunohistochemistry) , the ratio of the capillary number to fiber number (C/F), microstructure of gastrocnemius (HE stain) in the gastrocnemius muscle. Experiment results were analysed by the SPSS statistics software package (13.0). Results: (1) The results from hypoxia, weight after training, the activity of the serum CK or LDH could be matched to common condition. (2) Hypoxia and normoxia exercise increased the expression of VEGF in the gastrocnemius, and the repeated hypoxia caused the insensitivity of VEGF to hypoxia. The exercise with long time and common intensity induced the higher level VEGF expression than exercise with intermittence strong intensity. The living high-training low weakened the expression of VEGF induced by long time normal intensity exercise, and the group had shown the better exercise ability. The VEGF recovery and adaptation was inverse with its extent of rise, the order from the fast to the slow was: hypoxia, the living high-training low, normoxia exercise. The expression of VEGF was the early and quick response of the gastrocnemius after hypoxia and/or exercise. (3) Hypoxia and normoxia exercise increased the expression of VEGF in the gastrocnemius, the repeated hypoxia caused the insensitivity of VEGF to hypoxia. The skeletal muscle expression of bFGF induced by exercise was positively correlated with exercise intensity in a certain range with the characteristic delayed onset. The living high-training low with long time moderate intensity induced the higher level of bFGF expression than the corresponding normoxia, The living high-training low to increase progressively weakened the bFGF expression induced by high intensity of exercise. After hypoxia and/or exercise, the bFGF expression in the gastrocnemius was the delayed response. (4) On the 6th day of the short-term normoxia exercise and the living high-training low, the blood capillary neogenesis happened, which was more obviously in the living high-training low exercise than normoxia exercise, and more obviously in the long time moderate intensity exercise than the high intensity of exercise. The VEGF and bFGF expression induced by hypoxia and/or exercise was kept in the different time points. (5) The increased expression of the VEGF and bFGF presented during the whole reparation of EIMD, and bFGF was higher than that of VEGF. Both VEGF and bFGF had the synergistic effect on the reparation of EIMD.Conclusions: The exercise model used in the study is valid. The study based on the investigation of the VEGF and bFGF protein level, has revealed the regularity of the gastrocnemius muscle expression of VEGF and bFGF influenced by hypoxia and/or exercise. Either VEGF or bFGF may play a role in the capillary neogenesis of skeletal muscle and the reparation of EIMD. The short-time living high-training low could enhance the adaptation ability to rats' skeletal muscle to exercise with long-time and moderate intensity and exercise with intermittence strong intensity. There iswidely perspective of the study for hypoxia and/or exercise influencing VEGF andbFGF expression by different types of muscle fiber.