Eccentric Resistance Training Ameliorates Muscle Weakness in a Mouse Model of Idiopathic Inflammatory Myopathies
Eccentric Resistance Training Ameliorates Muscle Weakness in a Mouse Model of Idiopathic Inflammatory Myopathies
复制标题
DOI：
10.1002/art.41594
复制
发表时间：
2021-03-25
影响因子：
13.3
通讯作者：
Yamada, Takashi
中科院分区：
文献类型：
--
作者：
Himori, Koichi;Ashida, Yuki;Yamada, Takashi
目的 传统上，高力离心收缩（ECC）被排除在包括特发性炎症性肌病（IIM）患者在内的康复计划之外，因为未经证实的担心会导致肌肉损伤和炎症。在使用实验性自身免疫性肌炎（EAM）小鼠的IIM动物模型中，我们进行了这项研究，以探讨ECC训练是否可以安全有效地用于对抗IIM肌无力。方法通过注射3次弗氏完全佐剂乳化肌球蛋白免疫BALB/c小鼠诱导EAM。对照组 (n = 12) 和 EAM 小鼠 (n = 12) 接受 100 个 ECC 的急性训练或 4 周的 ECC 训练（每隔一天 20 个 ECC）。为了诱导 ECC，对足底屈肌进行电刺激，同时用力背屈踝关节。 结果 通过伊文思蓝染料摄取评估，在 100 次 ECC 急性发作后，与对照组相比，EAM 小鼠的肌肉细胞损伤较少 (P < 0.05)。 EAM 小鼠的带皮腓肠肌纤维的最大 Ca2+ 激活力降低，同时伴随内质网 (ER) 应激蛋白表达增加，包括 Gsp78 和 Gsp94 (P < 0.05)。 ECC 训练防止了力的下降和 ER 应激蛋白的增加，还增强了小热休克蛋白 (HSP) 的表达和肌原纤维结合 (P < 0.05)，从而稳定了肌原纤维的结构和功能。 结论 ECC 训练可以防止 IIM 小鼠模型中肌原纤维产生力的能力下降，这是通过抑制 ER 应激反应和小 HSP 介导的肌原纤维稳定来实现的。
Objective High-force eccentric contractions (ECCs) have traditionally been excluded from rehabilitation programs that include patients with idiopathic inflammatory myopathies (IIMs) due to unverified fear of causing muscle damage and inflammation. In an IIM animal model that used mice with experimental autoimmune myositis (EAM), we undertook this study to investigate whether ECC training can safely and effectively be used to counteract muscle weakness in IIM.Methods EAM was induced in BALB/c mice by immunization with 3 injections of myosin emulsified in Freund's complete adjuvant. Controls (n = 12) and mice with EAM (n = 12) were exposed to either an acute bout of 100 ECCs or 4 weeks of ECC training (20 ECCs every other day). To induce ECCs, plantar flexor muscles were electrically stimulated while the ankle was forcibly dorsiflexed.Results Less cell damage, as assessed by Evans blue dye uptake, was observed in the muscles of mice with EAM, compared to controls, after an acute bout of 100 ECCs (P < 0.05). Maximum Ca2+-activated force was decreased in skinned gastrocnemius muscle fibers from mice with EAM, and this was accompanied by increased expression of endoplasmic reticulum (ER) stress proteins, including Gsp78 and Gsp94 (P < 0.05). ECC training prevented the decrease in force and the increase in ER stress proteins and also enhanced the expression and myofibrillar binding of small heat-shock proteins (HSPs) (P < 0.05), which can stabilize myofibrillar structure and function.Conclusion ECC training protected against the reduction in myofibrillar force-generating capacity in an IIM mouse model, and this occurred via inhibition of ER stress responses and small HSP-mediated myofibrillar stabilization.