Adaptações morfológicas e respostas moleculares do músculo esquelético em modelo experimental de artrite reumatóide submetido ao exercício de força

Abstract

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.