Efeitos do exercício excêntrico na reabilitação do músculo esquelético de camundongos mdx após 3 e 21 dias de treinamento. Avaliações morfológica, funcional e molecular

Detalhes bibliográficos
Ano de defesa: 2019
Autor(a) principal: Pedrazzani, Paulo Silva
Orientador(a): Cornachione, Anabelle Silva lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de São Carlos
Câmpus São Carlos
Programa de Pós-Graduação: Programa de Pós-Graduação em Fisioterapia - PPGFt
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: https://repositorio.ufscar.br/handle/20.500.14289/11504
Resumo: Duchenne Muscular Dystrophy (DMD) is a degenerative genetic disease of a recessive nature linked to the mutation of the Xp21 region of the X chromosome. DMD is characterized by the absence of the protein dystrophin, which causes progressive muscle degeneration and weakness, resulting in death of the patient due to respiratory failure and or cardiac. Changes in the content of the myosin heavy chain (MHC) are commonly observed in dystrophic muscles and may be related to the greater fragility of this tissue. Because it is a progressive and disabling disease, physiotherapeutic resources such as physical exercise are commonly used to provide greater comfort for patients during disease progression. However, the major limitation is to determine the type and intensity of the exercise to be applied. For some time, eccentric exercise has been used in the rehabilitation of skeletal muscle after disuse, in the same way, studies show its effectiveness in the rehabilitation of dystrophic muscles, however, there are few reports in the scientific literature on the cellular and involved in the regeneration process. Therefore, the objective of this study is to analyze the molecular processes involved in the destruction of myofibers of mdx animals and to evaluate the consequences of the application of low intensity eccentric training for 21 days in the cytoarchitecture and in the contractile function of myofibers. Methods: Male mice aged 6 weeks, divided into 8 groups: sedentary mdx 3 days (mdxSED3) and sedentary mdx 21 days (mdxSED21) were used in this study; mdx trained 3 and 21 days, mdxTR3 and mdxTR21, respectively; wild type sedentary 3 and 21 days (wtSED3 and wtSED21) and finally, wild type trained 3 (wtTR3) and 21 days (wtTR21). After the training periods the animals were euthanized and blood samples were obtained for analysis of the enzyme creatine kinase (CK). Afterwards, both of the muscles were excised and subjected to functional analysis, for single fiber contraction force; morphology, for general aspects of the tissues; and morphometry, for the proportion of different types of fibers and tropism. Results: The single fiber strength analysis of the mdx mice showed a significant reduction when compared to the control group. In the morphological analysis it was possible to observe important alterations determined by the disease, such as: necrosis, increased connective tissue, nuclear centralization, among others. In the proportion of fibers, the dystrophic muscles presented a reduction in the number of types IIA fibers (FTIIA) concomitant to the increase of type I fibers (FTI), when compared to the respective controls. For trophic analysis, all types of fibers were observed in the youngest dystrophic group (3 days) while the oldest group (21 days) had a reduction in FTI and FTIIA fibers. After application of the low intensity eccentric training, it was possible to observe in the dystrophic muscles that the application of the exercise for 21 days was more effective in almost all aspects analyzed when compared to the more acute time (3 days). Conclusion: Our results suggest that eccentric exercise when applied at a low intensity for a longer period may be an effective therapeutic strategy to improve the functional, morphological and biochemical changes determined by the absence of the protein dystrophin.
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spelling Pedrazzani, Paulo SilvaCornachione, Anabelle Silvahttp://lattes.cnpq.br/0547232657871313http://lattes.cnpq.br/7843244578611831a4928e8a-3e99-49d0-afc5-7c65327247502019-07-16T17:13:39Z2019-07-16T17:13:39Z2019-05-16PEDRAZZANI, Paulo Silva. Efeitos do exercício excêntrico na reabilitação do músculo esquelético de camundongos mdx após 3 e 21 dias de treinamento. Avaliações morfológica, funcional e molecular. 2019. Dissertação (Mestrado em Fisioterapia) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/20.500.14289/11504.https://repositorio.ufscar.br/handle/20.500.14289/11504Duchenne Muscular Dystrophy (DMD) is a degenerative genetic disease of a recessive nature linked to the mutation of the Xp21 region of the X chromosome. DMD is characterized by the absence of the protein dystrophin, which causes progressive muscle degeneration and weakness, resulting in death of the patient due to respiratory failure and or cardiac. Changes in the content of the myosin heavy chain (MHC) are commonly observed in dystrophic muscles and may be related to the greater fragility of this tissue. Because it is a progressive and disabling disease, physiotherapeutic resources such as physical exercise are commonly used to provide greater comfort for patients during disease progression. However, the major limitation is to determine the type and intensity of the exercise to be applied. For some time, eccentric exercise has been used in the rehabilitation of skeletal muscle after disuse, in the same way, studies show its effectiveness in the rehabilitation of dystrophic muscles, however, there are few reports in the scientific literature on the cellular and involved in the regeneration process. Therefore, the objective of this study is to analyze the molecular processes involved in the destruction of myofibers of mdx animals and to evaluate the consequences of the application of low intensity eccentric training for 21 days in the cytoarchitecture and in the contractile function of myofibers. Methods: Male mice aged 6 weeks, divided into 8 groups: sedentary mdx 3 days (mdxSED3) and sedentary mdx 21 days (mdxSED21) were used in this study; mdx trained 3 and 21 days, mdxTR3 and mdxTR21, respectively; wild type sedentary 3 and 21 days (wtSED3 and wtSED21) and finally, wild type trained 3 (wtTR3) and 21 days (wtTR21). After the training periods the animals were euthanized and blood samples were obtained for analysis of the enzyme creatine kinase (CK). Afterwards, both of the muscles were excised and subjected to functional analysis, for single fiber contraction force; morphology, for general aspects of the tissues; and morphometry, for the proportion of different types of fibers and tropism. Results: The single fiber strength analysis of the mdx mice showed a significant reduction when compared to the control group. In the morphological analysis it was possible to observe important alterations determined by the disease, such as: necrosis, increased connective tissue, nuclear centralization, among others. In the proportion of fibers, the dystrophic muscles presented a reduction in the number of types IIA fibers (FTIIA) concomitant to the increase of type I fibers (FTI), when compared to the respective controls. For trophic analysis, all types of fibers were observed in the youngest dystrophic group (3 days) while the oldest group (21 days) had a reduction in FTI and FTIIA fibers. After application of the low intensity eccentric training, it was possible to observe in the dystrophic muscles that the application of the exercise for 21 days was more effective in almost all aspects analyzed when compared to the more acute time (3 days). Conclusion: Our results suggest that eccentric exercise when applied at a low intensity for a longer period may be an effective therapeutic strategy to improve the functional, morphological and biochemical changes determined by the absence of the protein dystrophin.Distrofia Muscular de Duchenne (DMD) é uma doença genética degenerativa de caráter recessivo ligada a mutação da região Xp21 do cromossomo X. A DMD se caracteriza pela ausência da proteína distrofina, que determina degeneração e fraqueza muscular progressivas, ocasionando óbito do paciente por falência respiratória e/ou cardíaca. Alterações no conteúdo da cadeia pesada da miosina (MHC) são comumente observadas em músculos distróficos e, podem estar relacionadas a maior fragilidade deste tecido. Por ser uma doença progressiva e incapacitante, recursos fisioterapêuticos como o exercício físico são comumente utilizados para proporcionar maior conforto para os pacientes durante a progressão da doença. Contudo, a grande limitação é determinar o tipo e a intensidade do exercício a ser aplicado. Há algum tempo o exercício excêntrico (EE) vem sendo utilizado na reabilitação do músculo esquelético após situações de desuso, da mesma forma, estudos mostram sua efetividade na reabilitação de músculos distróficos, porém, são poucos os relatos na literatura científica sobre os mecanismos celulares e moleculares envolvidos no processo de regeneração. Sendo assim, o objetivo deste estudo é analisar os processos moleculares envolvidos na destruição das miofibras dos animais mdx e, avaliar as consequências da aplicação do treinamento excêntrico de baixa intensidade, por 21 dias, na citoarquitetura e na função contrátil das miofibras. Métodos: Neste estudo foram utilizados camundongos machos com idade de 6 semanas, divididos em 8 grupos: mdx sedentários 3 dias (mdxSED3) e mdx sedentários 21 dias (mdxSED21); mdx treinados 3 e 21 dias, mdxTR3 e mdxTR21, respectivamente; wild type sedentários 3 e 21 dias (wtSED3 e wtSED21) e, wild type treinados 3 (wtTR3) e 21 dias (wtTR21). Após os períodos de treinamentos os animais foram eutanasiados e amostras sanguíneas foram obtidas para análise da enzima creatina quinase (CK). Em seguida ambos os músculos sóleos foram excisados e submetidos à análises de função, para força de contração de fibra única; morfologia, para aspectos gerais do tecidos; e morfometria, para proporção dos diferentes tipos de fibras e trofismo. Resultados: A análise de força de fibras únicas dos camundongos mdx mostraram redução significativa quando comparadas ao grupo controle. Na análise morfológica foi possível observar alterações importantes determinadas pela doença, tais como: necrose, aumento tecido conjuntivo, centralização nuclear, entre outras. Na proporção de fibras os músculos distróficos apresentaram redução do número de fibras tipo IIA (FTIIA) concomitante ao aumento de fibras do tipo I (FTI), quando comparados aos respectivos controles. Para análise do trofismo foi observado aumento de todas os tipos de fibras no grupo distrófico mais jovem (3 dias) enquanto o mais velho (21 dias) apresentou redução do mesmo nas fibras FTI e FTIIA. Após a aplicação do treinamento excêntrico de baixa intensidade foi possível observar, nos músculos distróficos, que a aplicação do exercício durante 21 dias foi mais efetiva em quase todos os aspectos analisados quando comparado ao tempo mais agudo (3 dias). Conclusão: Nossos resultados sugerem que o exercício do tipo excêntrico quando aplicado em uma intensidade baixa e por um período mais longo, pode ser uma estratégia terapêutica efetiva para melhorar as alterações funcional, morfológica e bioquímica determinada pela ausência da proteína distrofina.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP: 2017/00267-8porUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Fisioterapia - PPGFtUFSCarEnzima creatina quinase.TrofismoProporção dos diferentes tipos de fibrasFibra única.Exercício excêntricoCamundongos mdxDistrofia muscular de DuchenneCreatine kinase enzymeTropismProportion of different fiber typesSingle fiberEccentric exercisemdx miceDuchenne muscular dystrophyCIENCIAS DA SAUDE::FISIOTERAPIA E TERAPIA OCUPACIONALEfeitos do exercício excêntrico na reabilitação do músculo esquelético de camundongos mdx após 3 e 21 dias de treinamento. Avaliações morfológica, funcional e molecularEffects of eccentric exercise in rehab of the mdx muscle rehab after 3 and 21 days of training. 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dc.title.por.fl_str_mv Efeitos do exercício excêntrico na reabilitação do músculo esquelético de camundongos mdx após 3 e 21 dias de treinamento. Avaliações morfológica, funcional e molecular
dc.title.alternative.eng.fl_str_mv Effects of eccentric exercise in rehab of the mdx muscle rehab after 3 and 21 days of training. Morphological evaluations, functional and molecular
title Efeitos do exercício excêntrico na reabilitação do músculo esquelético de camundongos mdx após 3 e 21 dias de treinamento. Avaliações morfológica, funcional e molecular
spellingShingle Efeitos do exercício excêntrico na reabilitação do músculo esquelético de camundongos mdx após 3 e 21 dias de treinamento. Avaliações morfológica, funcional e molecular
Pedrazzani, Paulo Silva
Enzima creatina quinase.
Trofismo
Proporção dos diferentes tipos de fibras
Fibra única.
Exercício excêntrico
Camundongos mdx
Distrofia muscular de Duchenne
Creatine kinase enzyme
Tropism
Proportion of different fiber types
Single fiber
Eccentric exercise
mdx mice
Duchenne muscular dystrophy
CIENCIAS DA SAUDE::FISIOTERAPIA E TERAPIA OCUPACIONAL
title_short Efeitos do exercício excêntrico na reabilitação do músculo esquelético de camundongos mdx após 3 e 21 dias de treinamento. Avaliações morfológica, funcional e molecular
title_full Efeitos do exercício excêntrico na reabilitação do músculo esquelético de camundongos mdx após 3 e 21 dias de treinamento. Avaliações morfológica, funcional e molecular
title_fullStr Efeitos do exercício excêntrico na reabilitação do músculo esquelético de camundongos mdx após 3 e 21 dias de treinamento. Avaliações morfológica, funcional e molecular
title_full_unstemmed Efeitos do exercício excêntrico na reabilitação do músculo esquelético de camundongos mdx após 3 e 21 dias de treinamento. Avaliações morfológica, funcional e molecular
title_sort Efeitos do exercício excêntrico na reabilitação do músculo esquelético de camundongos mdx após 3 e 21 dias de treinamento. Avaliações morfológica, funcional e molecular
author Pedrazzani, Paulo Silva
author_facet Pedrazzani, Paulo Silva
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/7843244578611831
dc.contributor.author.fl_str_mv Pedrazzani, Paulo Silva
dc.contributor.advisor1.fl_str_mv Cornachione, Anabelle Silva
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/0547232657871313
dc.contributor.authorID.fl_str_mv a4928e8a-3e99-49d0-afc5-7c6532724750
contributor_str_mv Cornachione, Anabelle Silva
dc.subject.por.fl_str_mv Enzima creatina quinase.
Trofismo
Proporção dos diferentes tipos de fibras
Fibra única.
Exercício excêntrico
Camundongos mdx
Distrofia muscular de Duchenne
topic Enzima creatina quinase.
Trofismo
Proporção dos diferentes tipos de fibras
Fibra única.
Exercício excêntrico
Camundongos mdx
Distrofia muscular de Duchenne
Creatine kinase enzyme
Tropism
Proportion of different fiber types
Single fiber
Eccentric exercise
mdx mice
Duchenne muscular dystrophy
CIENCIAS DA SAUDE::FISIOTERAPIA E TERAPIA OCUPACIONAL
dc.subject.eng.fl_str_mv Creatine kinase enzyme
Tropism
Proportion of different fiber types
Single fiber
Eccentric exercise
mdx mice
Duchenne muscular dystrophy
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::FISIOTERAPIA E TERAPIA OCUPACIONAL
description Duchenne Muscular Dystrophy (DMD) is a degenerative genetic disease of a recessive nature linked to the mutation of the Xp21 region of the X chromosome. DMD is characterized by the absence of the protein dystrophin, which causes progressive muscle degeneration and weakness, resulting in death of the patient due to respiratory failure and or cardiac. Changes in the content of the myosin heavy chain (MHC) are commonly observed in dystrophic muscles and may be related to the greater fragility of this tissue. Because it is a progressive and disabling disease, physiotherapeutic resources such as physical exercise are commonly used to provide greater comfort for patients during disease progression. However, the major limitation is to determine the type and intensity of the exercise to be applied. For some time, eccentric exercise has been used in the rehabilitation of skeletal muscle after disuse, in the same way, studies show its effectiveness in the rehabilitation of dystrophic muscles, however, there are few reports in the scientific literature on the cellular and involved in the regeneration process. Therefore, the objective of this study is to analyze the molecular processes involved in the destruction of myofibers of mdx animals and to evaluate the consequences of the application of low intensity eccentric training for 21 days in the cytoarchitecture and in the contractile function of myofibers. Methods: Male mice aged 6 weeks, divided into 8 groups: sedentary mdx 3 days (mdxSED3) and sedentary mdx 21 days (mdxSED21) were used in this study; mdx trained 3 and 21 days, mdxTR3 and mdxTR21, respectively; wild type sedentary 3 and 21 days (wtSED3 and wtSED21) and finally, wild type trained 3 (wtTR3) and 21 days (wtTR21). After the training periods the animals were euthanized and blood samples were obtained for analysis of the enzyme creatine kinase (CK). Afterwards, both of the muscles were excised and subjected to functional analysis, for single fiber contraction force; morphology, for general aspects of the tissues; and morphometry, for the proportion of different types of fibers and tropism. Results: The single fiber strength analysis of the mdx mice showed a significant reduction when compared to the control group. In the morphological analysis it was possible to observe important alterations determined by the disease, such as: necrosis, increased connective tissue, nuclear centralization, among others. In the proportion of fibers, the dystrophic muscles presented a reduction in the number of types IIA fibers (FTIIA) concomitant to the increase of type I fibers (FTI), when compared to the respective controls. For trophic analysis, all types of fibers were observed in the youngest dystrophic group (3 days) while the oldest group (21 days) had a reduction in FTI and FTIIA fibers. After application of the low intensity eccentric training, it was possible to observe in the dystrophic muscles that the application of the exercise for 21 days was more effective in almost all aspects analyzed when compared to the more acute time (3 days). Conclusion: Our results suggest that eccentric exercise when applied at a low intensity for a longer period may be an effective therapeutic strategy to improve the functional, morphological and biochemical changes determined by the absence of the protein dystrophin.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-07-16T17:13:39Z
dc.date.available.fl_str_mv 2019-07-16T17:13:39Z
dc.date.issued.fl_str_mv 2019-05-16
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv PEDRAZZANI, Paulo Silva. Efeitos do exercício excêntrico na reabilitação do músculo esquelético de camundongos mdx após 3 e 21 dias de treinamento. Avaliações morfológica, funcional e molecular. 2019. Dissertação (Mestrado em Fisioterapia) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/20.500.14289/11504.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/20.500.14289/11504
identifier_str_mv PEDRAZZANI, Paulo Silva. Efeitos do exercício excêntrico na reabilitação do músculo esquelético de camundongos mdx após 3 e 21 dias de treinamento. Avaliações morfológica, funcional e molecular. 2019. Dissertação (Mestrado em Fisioterapia) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/20.500.14289/11504.
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