Resposta de diferentes músculos de um modelo experimental para distrofia muscular de Duchenne após exacerbação da doença pelo exercício físico
Data
2024-11-18
Autores
Costa, Pietra Mascarenhas Souza 
Orientadores
De Oliveira, Flavia
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: A distrofia muscular de Duchenne (DMD) é uma doença ainda sem cura, caracterizada por necrose muscular progressiva. Sabe-se que no músculo distrófico, as fibras musculares do tipo I (de contração lenta) são mais resistentes à necrose e, em contraponto, as fibras tipo II (de contração rápida) são mais vulneráveis ao dano muscular induzido pelo exercício. O m. tibial anterior possui predominantemente fibras do tipo rápidas, enquanto o m. sóleo possui predominância de fibras do tipo lentas. Objetivo: Investigar os achados morfométricos e histopatológicos de músculos com diferentes composições de predominância de tipos de fibras musculares (tibial anterior e sóleo) em camundongos mdx submetidos à exacerbação da doença por protocolo de exercício físico em esteira. Material e métodos: Camundongos C57BL10-DMD/mdx com 8 meses de vida foram distribuídos em dois grupos: Mdx sedentário (Mdx-S) e Mdx+exercício (Mdx-T), sendo que para o m. tibial anterior, acrescentou-se TA à sigla (Mdx-S-TA e Mdx-T-TA) e, para o sóleo, acrescentou-se S a sigla (Mdx-S-S e Mdx-T-S). Somente o grupo Mdx-T foi submetido ao protocolo de exercício por 8 semanas. Os mm. tibial anterior e sóleo foram avaliados quanto à análise morfométrica (densidade e área das fibras musculares) e histopatológica qualitativa e semiquantitativa (área de degeneração-inflamação, regeneração e infiltrado inflamatório). Os dados foram comparados por meio do teste t de Student para análise da variável exercício em cada músculo, e foi adotado para ambos os músculos (em mdx-T e Mdx-S) n=8 na análise morfométrica e n=6 na análise histopatológica. Resultados: A análise morfométrica da média da densidade celular do m. tibial anterior entre grupo Mdx-S-TA e Mdx-T-TA, assim como do m. sóleo entre Mdx-S-S e Mdx-T-S, não apresentou diferença na comparação. A análise morfométrica da área das fibras do m. tibial anterior mostrou que entre grupo Mdx-S-TA e Mdx-T-TA, assim como a análise da área das fibras do m. sóleo entre Mdx-S-S e Mdx-T-S, não houve diferença na área das fibras entre os grupos. Na frequência de distribuição das diferentes áreas encontradas e na análise histopatológica qualitativa, observou-se que há heterogeneidade na área das fibras de ambos os músculos, e maior heterogeneidade em TA (em Mdx-S e Mdx-T). Com relação a análise histopatológica semiquantitativa (em %), não houve diferença na comparação da média da área de degeneração no m. tibial anterior e m. sóleo entre grupo Mdx-S e Mdx-T. Na comparação das médias da área de inflamação no m. tibial anterior entre grupo Mdx-S-TA e Mdx-T-TA não houve diferença entre os grupos comparados. Já no m.sóleo, Mdx-T-S apresentou menor porcentagem de inflamação que o grupo Mdx-S-S. Na comparação da média da área de regeneração, Mdx-T-TA apresentou maior regeneração que o grupo Mdx-S-TA. No m. sóleo, entre grupo Mdx-S-S e Mdx-T-S, não houve diferença entre os grupos comparados para área de regeneração. Conclusão: Os músculos investigados não apresentaram alterações morfométricas quando submetidos ao exercício, a fim de exacerbar a doença. O m. tibial anterior apresenta maior acometimento na resposta de cada músculo ao exercício. Ademais, o exercício intenso diminuiu a inflamação, causando efeito positivo no m.sóleo. Assim, esse estudo traz informações relevantes sobre as interferências das diferentes predominâncias de fibras (tipo I e II) em estágios avançados da doença e que podem ser utilizadas para tratamentos futuros.
Introduction: Duchenne muscular dystrophy (DMD) is an incurable disease characterized by progressive muscle necrosis. It is known that in dystrophic muscle, type I (slow-twitch) muscle fibers are more resistant to necrosis, while type II (fast-twitch) fibers are more vulnerable to exercise-induced muscle damage. The anterior tibialis muscle predominantly contains fasttwitch fibers, while the soleus muscle is primarily composed of slow-twitch fibers. Objective: To investigate the morphometric and histopathological findings of muscles with different fiber type compositions (anterior tibialis and soleus) in mdx mice subjected to disease exacerbation through a treadmill exercise protocol. Materials and Methods: C57BL10- DMD/mdx mice aged 8 months were divided into two groups: sedentary Mdx (Mdx-S) and exercised Mdx (Mdx-T). For the anterior tibial muscle, the designation "TA" was added (MdxS-TA and Mdx-T-TA), and for the soleus muscle, "S" was added (Mdx-S-S and Mdx-T-S). Only the Mdx-T group underwent an exercise protocol for 8 weeks. The anterior tibial and soleus muscles were evaluated for morphometric analysis (muscle fiber density and area) and qualitative and semi-quantitative histopathological analysis (degeneration-inflammation area, regeneration, and inflammatory infiltrate). Data were compared using the Student's t-test to analyze the exercise variable in each muscle, with n=8 for morphometric analysis and n=6 for histopathological analysis in both Mdx-T and Mdx-S groups. Results: Morphometric analysis of the average cellular density of the anterior tibial muscle (TA) between the Mdx-S-TA and Mdx-T-TA groups, as well as the soleus muscle (S) between the Mdx-S-S and Mdx-T-S groups, showed no difference in comparison. The morphometric analysis of fiber area in the anterior tibial muscle showed that there was no difference in fiber area between the Mdx-S-TA and Mdx-T-TA groups, nor in the soleus muscle between the Mdx-S-S and Mdx-T-S groups. In the distribution frequency of the different areas found and the qualitative histopathological analysis, it was observed that there is heterogeneity in the fiber area of both muscles, with greater heterogeneity in the TA (in both Mdx-S and Mdx-T). Regarding the semi-quantitative histopathological analysis (in %), no difference was found in the comparison of the mean degeneration area in the anterior tibial and soleus muscles between the Mdx-S and Mdx-T groups. In the comparison of the mean inflammation area in the anterior tibial muscle between the Mdx-S-TA and Mdx-T-TA groups, no difference was observed. However, in the soleus muscle, the Mdx-T-S group showed a lower percentage of inflammation than the Mdx-S-S group. In the comparison of the mean regeneration area, the Mdx-T-TA group showed greater regeneration than the Mdx-S-TA group. In the soleus muscle, between the Mdx-S-S and MdxT-S groups, there was no difference between the groups in the regeneration area. Conclusion: The muscles investigated did not show morphometric changes when subjected to exercise intended to exacerbate the disease. The anterior tibial muscle showed more involvement in the response of each muscle to exercise. Moreover, intense exercise decreased inflammation, having a positive effect on the soleus muscle. Therefore, this study provides relevant information about the impact of different fiber type predominances (Type I and II) in the advanced stages of the disease, which can be useful for future treatments.
Introduction: Duchenne muscular dystrophy (DMD) is an incurable disease characterized by progressive muscle necrosis. It is known that in dystrophic muscle, type I (slow-twitch) muscle fibers are more resistant to necrosis, while type II (fast-twitch) fibers are more vulnerable to exercise-induced muscle damage. The anterior tibialis muscle predominantly contains fasttwitch fibers, while the soleus muscle is primarily composed of slow-twitch fibers. Objective: To investigate the morphometric and histopathological findings of muscles with different fiber type compositions (anterior tibialis and soleus) in mdx mice subjected to disease exacerbation through a treadmill exercise protocol. Materials and Methods: C57BL10- DMD/mdx mice aged 8 months were divided into two groups: sedentary Mdx (Mdx-S) and exercised Mdx (Mdx-T). For the anterior tibial muscle, the designation "TA" was added (MdxS-TA and Mdx-T-TA), and for the soleus muscle, "S" was added (Mdx-S-S and Mdx-T-S). Only the Mdx-T group underwent an exercise protocol for 8 weeks. The anterior tibial and soleus muscles were evaluated for morphometric analysis (muscle fiber density and area) and qualitative and semi-quantitative histopathological analysis (degeneration-inflammation area, regeneration, and inflammatory infiltrate). Data were compared using the Student's t-test to analyze the exercise variable in each muscle, with n=8 for morphometric analysis and n=6 for histopathological analysis in both Mdx-T and Mdx-S groups. Results: Morphometric analysis of the average cellular density of the anterior tibial muscle (TA) between the Mdx-S-TA and Mdx-T-TA groups, as well as the soleus muscle (S) between the Mdx-S-S and Mdx-T-S groups, showed no difference in comparison. The morphometric analysis of fiber area in the anterior tibial muscle showed that there was no difference in fiber area between the Mdx-S-TA and Mdx-T-TA groups, nor in the soleus muscle between the Mdx-S-S and Mdx-T-S groups. In the distribution frequency of the different areas found and the qualitative histopathological analysis, it was observed that there is heterogeneity in the fiber area of both muscles, with greater heterogeneity in the TA (in both Mdx-S and Mdx-T). Regarding the semi-quantitative histopathological analysis (in %), no difference was found in the comparison of the mean degeneration area in the anterior tibial and soleus muscles between the Mdx-S and Mdx-T groups. In the comparison of the mean inflammation area in the anterior tibial muscle between the Mdx-S-TA and Mdx-T-TA groups, no difference was observed. However, in the soleus muscle, the Mdx-T-S group showed a lower percentage of inflammation than the Mdx-S-S group. In the comparison of the mean regeneration area, the Mdx-T-TA group showed greater regeneration than the Mdx-S-TA group. In the soleus muscle, between the Mdx-S-S and MdxT-S groups, there was no difference between the groups in the regeneration area. Conclusion: The muscles investigated did not show morphometric changes when subjected to exercise intended to exacerbate the disease. The anterior tibial muscle showed more involvement in the response of each muscle to exercise. Moreover, intense exercise decreased inflammation, having a positive effect on the soleus muscle. Therefore, this study provides relevant information about the impact of different fiber type predominances (Type I and II) in the advanced stages of the disease, which can be useful for future treatments.
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Citação
COSTA, Pietra Mascarenhas Souza. Resposta de diferentes músculos de um modelo experimental para distrofia muscular de Duchenne após exacerbação da doença pelo exercício físico. 2024. 37 f. Trabalho de conclusão de curso (Graduação em Fisioterapia) - Universidade Federal de São Paulo, Instituto de Saúde e Sociedade, Santos, 2024.