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Effects And Mechanisms Of Hypoxia Or Training On The Angiogenesis Of Capillary And Expressions Of VEGF And HIF-1a In The Skeletal Muscle Of Rats

Posted on:2005-04-26Degree:DoctorType:Dissertation
Country:ChinaCandidate:S S MaoFull Text:PDF
GTID:1117360125467187Subject:Exercise Physiology
Abstract/Summary:PDF Full Text Request
IntroductionIt is supposed recently that the HiLo (Live High-Train Low) model, an approach to altitude training by living high while simultaneously training at low elevation, be able to improve one's endurance performance. Some researches speculate that the increased ability for competition may largely depend on the functions of skeletal muscles rather than that of hearts and lungs. As a result, an increasing attention has been paid to the studies on skeletal muscles.It is known that exposure to altitude may have biological compensatory effects on histology, blood kinetics, and substrate metabolizing that enhances oxygen transport, substrate oxidation and tissue growth. The angiogenesis of capillary is an important pattern of compensation in skeletal muscles, which would alleviate the limitation of tissue oxygen diffusion. This produces the increase of muscular oxygen consumption, which improves one's performance under hypoxic conditions. So the angiogenesis of capillary contributes one possible type of adaptation to the hypoxic condition in skeletal muscles.However, whether hypoxic stimulus promotes the growth of capillary remains controversy in the literature. Though some researchers support that chronic hypoxia training would produce greater capillary growth than normoxic training, there lacks conclusive evidence that the HiLo would increase mammal skeletal muscular capillary (SMC).Within the last decade, many factors have been found to be able to influence the formation of new capillaries, among which VEGF seems to be the most important mediator of hypoxia-induced angiogenesis. VEGF exists in a variety of cells but is mainly distributed among skeletal muscular capillary. It suggests that VEGF and its gene expressions plays an important role in the growth of new capillary under hypoxic conditions. There are a few possible mechanisms that hypoxia influence the VEGF expressions, one of which is the effect of hypoxia on HIF-1. Recently, an amount of evidences supports that hypoxia induces the transcription of VEGF through mediated O2-responsive transcriptional factor, HIF-1. That is, though the mechanism of angiogenesis is undefined so far, it may involve the HIF-1 transcription factor, especially the regulatory (-subunit of HIF-1 (HIF-1(). Therefore, to investigate the molecular biological mechanisms of the angiogenesis under hypoxia or training-stimulus, it is imperative to study the expressions of the central transcription factor HIF-1(.In short, the angiogenesis of skeletal muscular capillary (SMC) seems to be an essential adaptation in histological mechanism. Could either hypoxia or training induce angiogenesis of skeletal muscles? How does hypoxia in addition to exercises influence the formation of new capillary in skeletal muscles? Many mechanisms concerning to these questions remain unidentified, though it is asserted that both VEGF and HIF-1 involve in the mechanism of microvessel angiogenesis responses to hypoxia and/or training.2. Experimental Methods and PurposeHence, in this study, experiments were conducted for hypoxic conditions and normoxic training modes. Then the tissues that were separated for examinations were the gastrocnemius muscle of the experimental rats. According to the different protocols, expressions of protein and gene of HIF-1( and VEGF were measured by means of molecular biology, histochemistry and immunology. At the meantime, using light microscopy, some morphometric indexes were obtained, including CD, C/F and FCSA. The purpose of present study is to investigate SMC responses to hypoxia / training using rats as substitutes. Possible molecular mechanisms are proposed to interpret the results, which help understand the effects of hypoxia / normoxic training and prevent acute altitude illness or hypoxic trauma.3. Conclusions3.1In general, there has been a dynamic trend among angiogenesis responses of SMC, fromwhich hypoxia / normoxic training result.Hypothesis 1 and 2 in the preface are supported, while hypothesis 3 only is partly...
Keywords/Search Tags:skeletal muscle, hypoxia, training, angiogenesis, HIF-1(, VEGF, gene and protein expressions
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