Graduate School of Health Sciences, Sapporo Medical University , Sapporo , Japan.
J Appl Physiol (1985). 2019 Jul 1;127(1):71-80. doi: 10.1152/japplphysiol.00102.2019. Epub 2019 May 16.
Patients with rheumatoid arthritis (RA) frequently suffer from muscle weakness. We examined whether eccentric training prevents skeletal muscle weakness in adjuvant-induced arthritis (AIA) rat, a widely used animal model for RA. AIA was induced in the knees of Wistar rats by injection of complete Freund's adjuvant. To induce eccentric contractions (ECCs), neuromuscular electrical stimulation (45 V) was applied to the plantar flexor muscles simultaneously with forced dorsiflexion of the ankle joint (0-40°) and was given every 6 s. ECC exercise was applied every other day for a total of 11 sessions and consisted of 4 sets of 5 contractions. There was a significant reduction in in vitro maximum Ca-activated force in skinned fibers in gastrocnemius muscle from AIA rats. These changes were associated with reduced expression levels of contractile proteins (i.e., myosin and actin), increased levels of inflammation redox stress-related biomarkers (i.e., TNF-α, malondialdehyde-protein adducts, NADPH oxidase 2, and neuronal nitric oxide synthase), and autolyzed active calpain-1 in AIA muscles. ECC training markedly enhanced the steady-state levels of αB-crystallin, a small heat shock protein, and its binding to the myofibrils and prevented the AIA-induced myofibrillar dysfunction, reduction in contractile proteins, and inflammation-oxidative stress insults. Our findings demonstrate that ECC training preserves myofibrillar function without muscle damage in AIA rats, which is at least partially attributable to the protective effect of αB-crystallin on the myofibrils against oxidative stress-mediated protein degeneration. Thus ECC training can be a safe and effective intervention, counteracting the loss of muscle strength in RA patients. Eccentric contractions (ECCs) are regarded as an effective way to increase muscle strength. No studies, however, assess safety and effectiveness of ECC training on muscle weakness associated with rheumatoid arthritis. Here, we used adjuvant-induced arthritis (AIA) rats to demonstrate that ECC training prevents intrinsic contractile dysfunction without muscle damage in AIA rats, which may be attributed to the protective effect of αB-crystallin on the myofibrils against inflammation-oxidative stress insults.
类风湿关节炎（RA）患者常出现肌肉无力。我们研究了电刺激离心收缩（ECC）训练是否能预防佐剂诱导关节炎（AIA）大鼠的骨骼肌无力，AIA 是一种广泛用于 RA 的动物模型。通过向 Wistar 大鼠膝关节注射完全弗氏佐剂诱导 AIA。为了诱导离心收缩（ECC），同时对踝关节进行强制背屈（0-40°），向足底屈肌施加神经肌肉电刺激（45V），每 6s 进行一次。ECC 运动每隔一天进行一次，共进行 11 次，每次包括 4 组 5 次收缩。AIA 大鼠比目鱼肌中经皮纤维的最大 Ca 激活力显著降低。这些变化与收缩蛋白（肌球蛋白和肌动蛋白）表达水平降低、炎症氧化应激相关生物标志物（TNF-α、丙二醛-蛋白加合物、NADPH 氧化酶 2 和神经元型一氧化氮合酶）水平升高以及 AIA 肌肉中自溶活性钙蛋白酶-1 有关。ECC 训练显著增强了小热休克蛋白 αB-晶体蛋白的稳态水平及其与肌原纤维的结合，并防止了 AIA 引起的肌原纤维功能障碍、收缩蛋白减少和炎症氧化应激损伤。我们的研究结果表明，ECC 训练可在 AIA 大鼠中保持肌原纤维功能而不引起肌肉损伤，这至少部分归因于 αB-晶体蛋白对肌原纤维的保护作用，防止氧化应激介导的蛋白变性。因此，ECC 训练可以是一种安全有效的干预措施，对抗 RA 患者的肌肉力量丧失。ECC 是增加肌肉力量的有效方法。然而，目前尚无研究评估 ECC 训练对与类风湿关节炎相关的肌肉无力的安全性和有效性。在这里，我们使用佐剂诱导的关节炎（AIA）大鼠来证明 ECC 训练可预防内在收缩功能障碍而不引起肌肉损伤，这可能归因于 αB-晶体蛋白对肌原纤维的保护作用，防止炎症氧化应激损伤。
