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Adaptações morfológicas e respostas moleculares do músculo esquelético em modelo experimental de artrite reumatóide submetido ao exercício de forçaExercício resistidoHipertrofia muscularInflamaçãoAtrofia muscularResistance exerciseMuscle hypertrophyInflammationMuscle atrophyEducação FísicaIntrodução: durante a artrite reumatóide (AR) há perda significativa da massa muscular (caquexia reumatóide) resultante principalmente do processo inflamatório crônico e consequente aumento de proteínas catabólicas (MurF-1, atrogina e miostatina). O exercício de força (EF) é um conhecido promotor do crescimento muscular que ocorre em decorrência de sinalizações moleculares que estimulam a ativação das células satélites por meio de proteínas anabólicas (IGF-1, MyoD e miogenina). No entanto, as respostas moleculares do músculo esquelético induzidas pelo EF durante o processo inflamatório crônico não são totalmente conhecidas. Objetivo: avaliar as respostas moleculares envolvidas no anabolismo e catabolismo do músculo esquelético após estímulo agudo de EF em ratos induzidos à AR. Metodologia: participaram do estudo 32 ratos Wistar, fêmeas (8 semanas, 126 ± 24g), divididas em quatro grupos: grupo controle (GCT, n=8); grupo exercício (GEx, n=8); grupo artrite (GAR, n=8) e grupo artrite + exercício (GAR+Ex, n=8). O protocolo de indução de AR foi realizado com duas injeções aplicadas subcutaneamente e uma nas articulações dos tornozelos das patas traseiras, separadas por intervalos de sete dias. Após 15 dias, os animais foram submetidos a uma sessão de EF (protocolo de escalada) e 6 horas após foram eutanasiados. As manifestações externas da doença (perimetria articular e escore de inflamação), assim como, o peso e a ingestão de ração foram avaliados continuamente nos grupos artrite (AR) e controle (CT). A área de secção transversa (AST) das fibras dos músculos gastrocnêmios foi analisada em 200 células pelo método hematoxilina e eosina. No músculo Gastrocnêmio foram analisadas as expressões de RNA mensageiro (RNAm) de IGF-1, MyoD, Miogenina, Miostatina, Murf-1, atrogina e GAPDH (controle endógeno) pelo método PCR quantitativo em tempo real e calculados pelo método de Livak (ΔΔCT). A comparação entre grupos foi feita por ANOVA one-way e test t independente. Os valores contínuos foram analisados por ANOVA de medidas repetidas (comparações intra grupos x momentos). Os dados são apresentados como média e erro padrão da média (SEM). O nível de significância adotada foi p≤0,05. Resultados: o protocolo de indução gerou aumento nos indicadores externos da doença (p<0,001) além de reduções na AST e peso úmido do músculo gastrocnêmio (p≤ 0,05). Foram observados aumentos nos níveis de RNAm de miostatina (4,5 vezes), atrogina (2,5 vezes), MyoD (3,7 vezes) e miogenina (5 vezes) no grupo GAR. O grupo GAR+Ex não apresentou alterações de miostatina e atrogina, e reduziu os níveis de Murf-1 (60%). A expressão de miogenina aumentou no grupo GEx (4 vezes). Conclusão: concluímos que a AR induziu atrofia muscular concomitantemente com aumentos nos níveis de RNAm de Miogenina, MyoD, Miostatina e atrogina. Uma sessão de EF foi capaz de normalizar a expressão de RNAm de miostatina e atrogina e reduzir Murf-1 em ratas induzidas à AR.Introduction: During rheumatoid arthritis (RA) the loss of muscle mass (rheumatoid cachexia) occurs due to chronic inflammation and consequent increase in catabolic proteins (Murf-1, myostatin and atrogin). Resistance exercise (RE) is a well kwon intervention which promotes muscle mass gains that occurs as a result of molecular signal of satellite cells through proteins anabolic (IGF-1, MyoD and miogenin). However, skeletal muscle molecular response induced by RE in presence of RA are not well elucidated. Objectives: To analyze skeletal muscle anabolism and catabolism responses to an animal experimental model of RA submitted to an acute bout of RE. Methods: 32 females Wistar rats (8 weeks, 126 ± 24g) were randomic allocated into four groups, control group (GCT, n=8), exercise group (GEx, n=8), control arthritis group (GAR, n=8) and arthritis plus exercise group (GAR+Ex, n=8). The RA induced protocols were conducted with two subcutaneous injections applications and one in the hind paws ankles, with intervals of seven days between applications. After 15 days the animals were submitted to an acute bout of RE (climb protocol) and six hours post protocol animals were euthanized. The external manifestations of RA (perimeter joint and inflammation score), as well as animal weight and feed intake were evaluated throughout the study in the arthritis (AR) and control (CT) groups. The cross-sectional area (CSA) fibers of the gastrocnêmio muscle were analyzed in 200 cells by hematoxylin and eosin method. The gastrocnemius muscle mRNA expression of IGF-1, MyoD, Myogenin, myostatin, Murf-1, atrogin and GAPDH (endogenous control) were analyzed by quantitative real time PCR followed by Livak method (ΔΔCT). Data are present by mean and standard error mean (SEM), groups comparisons were performed by one-way ANOVA (Comparisons between groups), repeated measures ANOVA (Comparisons within groups x Moments) and test t independent. Alpha level was significant when p≤0.05. Results: The RA induction protocol increased external manifestations (p <0.001) and reduced CSA and wet weight of gastrocnemiu muscle (p ≤ 0.05).Increased mRNA levels of Myostatin (4.5 fold), atrogin (2.5 fold), MyoD (3.7-fold) and Myogenin (5 fold) were only observed in the GAR group. The GAR+Ex group reduced mRNA levels of Murf-1 (60%) and no changes were observed in myostatin and atrogin. The GEx group increased mRNA levels of myogenin (4 fold). Conclusion: We concluded that RA induced muscle atrophy and increased mRNA levels of Miogenin, MyoD, Miostatin and atrogin, although an acute bout of RE was efficient to normalize mRNA levels of Miostatin and atrogin and reduced Murf-1 in female rats RA induced.Universidade Federal do Triângulo MineiroInstituto de Ciências da Saúde - ICS::Curso de Graduação em Educação FísicaBrasilUFTMPrograma de Pós-Graduação em Educação FísicaORSATTI, Fábio Lera27865522819http://lattes.cnpq.br/2185904879371466OLIVEIRA, Anselmo Alves de2016-02-23T17:02:21Z2014-12-11info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfOLIVEIRA, Anselmo Alves de. Adaptações morfológicas e respostas moleculares do músculo esquelético em modelo experimental de artrite reumatoide submetido ao exercício de força. 2014. 53 f. 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Cell Mol Life Sci, v. 70, n. 21, p. 4117-30, Nov 2013.http://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFTMinstname:Universidade Federal do Triangulo Mineiro (UFTM)instacron:UFTM2018-03-23T18:57:30Zoai:bdtd.uftm.edu.br:tede/209Biblioteca Digital de Teses e Dissertaçõeshttp://bdtd.uftm.edu.br/PUBhttp://bdtd.uftm.edu.br/oai/requestbdtd@uftm.edu.br||bdtd@uftm.edu.bropendoar:2024-04-24T09:59:01.068652Biblioteca Digital de Teses e Dissertações da UFTM - Universidade Federal do Triangulo Mineiro (UFTM)false
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