Low-frequency electrical stimulation alleviates immobilization-evoked disuse muscle atrophy by repressing autophagy in skeletal muscle of rabbits

Liu, A-Ying; Zhang, Quan-Bing; Zhu, Hua-Long; Xiong, Yun; Wang, Feng; Huang, Pengpeng; Xu, Qi-Yu; Zhong, Huazhang; Wang, Hua; Zhou, Yun

doi:10.1186/s12891-022-05350-5

Cited by 7 publications

(6 citation statements)

References 56 publications

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“…In order to observe the natural process of joint contracture, we established an animal model using immobilization by aluminum plates. Joint contracture is characterized by a reduction of joint range of motion compared with normal joints [ 34 , 35 ], thus decreased join range of motion represents increased degree of joint contracture. Previous studies have suggested that joint contracture occur within 1 week of knee joint immobilization and progress in a time-dependent manner [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Role of hypoxia-mediated pyroptosis in the development of extending knee joint contracture in rats

Zhang,

Huo,

et al. 2024

Eur J Med Res

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Joint contracture is one of the common diseases clinically, and joint capsule fibrosis is considered to be one of the most important pathological changes of joint contracture. However, the underlying mechanism of joint capsule fibrosis is still controversial. The present study aims to establish an animal model of knee extending joint contracture in rats, and to investigate the role of hypoxia-mediated pyroptosis in the progression of joint contracture using this animal model. 36 male SD rats were selected, 6 of which were not immobilized and were used as control group, while 30 rats were divided into I-1 group (immobilized for 1 week following 7 weeks of free movement), I-2 group (immobilized for 2 weeks following 6 weeks of free movement), I-4 group (immobilized for 4 weeks following 4 weeks of free movement), I-6 group (immobilized for 6 weeks following 2 weeks of free movement) and I-8 group (immobilized for 8 weeks) according to different immobilizing time. The progression of joint contracture was assessed by the measurement of knee joint range of motion, collagen deposition in joint capsule was examined with Masson staining, protein expression levels of HIF-1α, NLRP3, Caspase-1, GSDMD-N, TGF-β1, α-SMA and p-Smad3 in joint capsule were assessed using western blotting, and the morphological changes of fibroblasts were observed by transmission electron microscopy. The degree of total and arthrogenic contracture progressed from the first week and lasted until the first eight weeks after immobilization. The degree of total and arthrogenic contracture progressed rapidly in the first four weeks after immobilization and then progressed slowly. Masson staining indicated that collagen deposition in joint capsule gradually increased in the first 8 weeks following immobilization. Western blotting analysis showed that the protein levels of HIF-1α continued to increase during the first 8 weeks of immobilization, and the protein levels of pyroptosis-related proteins NLRP3, Caspase-1, GSDMD-N continued to increase in the first 4 weeks after immobilization and then decreased. The protein levels of fibrosis-related proteins TGF-β1, p-Smad3 and α-SMA continued to increase in the first 8 weeks after immobilization. Transmission electron microscopy showed that 4 weeks of immobilization induced cell membrane rupture and cell contents overflow, which further indicated the activation of pyroptosis. Knee extending joint contracture animal model can be established by external immobilization orthosis in rats, and the activation of hypoxia-mediated pyroptosis may play a stimulating role in the process of joint capsule fibrosis and joint contracture.

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Section: Discussionmentioning

confidence: 99%

Role of hypoxia-mediated pyroptosis in the development of extending knee joint contracture in rats

Zhang,

Huo,

et al. 2024

Eur J Med Res

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“…Parkin-mediated mitophagy is one of the most important mitophagy pathways, and COXIV is a well-known mitophagy marker protein 25 . Previous studies suggested that protein levels of LC3B-II increased after IM, and electrical stimulation can inhibit the overexpression of LC3B-II 19 . In this study, the activation of mitophagy on the muscles after IM could be detected by examining the upregulation of Parkin and the down-regulation of COXIV.…”

Section: Discussionmentioning

confidence: 87%

“…25 Previous studies suggested that protein levels of LC3B-II increased after IM, and electrical stimulation can inhibit the overexpression of LC3B-II. 19 In this study, the activation of mitophagy on the muscles after IM could be detected by examining the upregulation of Parkin and the down-regulation of COXIV. Moreover, the expression of Parkin reached the highest level and the expression of COXIV reached the lowest level at 2 wks after IM, which indicated that Parkin-mediated mitophagy attained to the highest level at 2 wks after IM.…”

Section: Discussionmentioning

confidence: 97%

“…2 A previous study has documented that electrical stimulation can improve IM-induced reductions in joint ranges of motion and alleviate skeletal muscle atrophy. 19 Nevertheless, the exact mechanism underlying the therapeutic effect still remains unclear. In this experiment, plaster casts were used to establish animal model of knee contracture and skeletal muscle atrophy.…”

Section: Discussionmentioning

confidence: 99%

“…Muscle atrophy is one of the most important aspects of myogenic contracture, which can contribute to restricted joint ranges of motion 2 . A previous study has documented that electrical stimulation can improve IM-induced reductions in joint ranges of motion and alleviate skeletal muscle atrophy 19 . Nevertheless, the exact mechanism underlying the therapeutic effect still remains unclear.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Electrical Stimulation on Disuse Muscular Atrophy Induced by Immobilization

Zhang¹,

Liu²,

Fang

et al. 2023

Am J Phys Med Rehabil

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Objectives The aims of the study are to investigate the effect of electrical stimulation on disuse muscular atrophy induced by immobilization (IM) and to explore the role of PERK signal and Parkin-dependent mitophagy in this process. Design In the first subexperiment, 24 rabbits were divided into four groups, which underwent different periods of IM. In the second subexperiment, 24 rabbits were divided into four groups on average in accordance with different kinds of interventions. To test the time-dependent changes of rectus femoris after IM, and to evaluate the effect of electrical stimulation, the wet weights, cross-sectional area and fat deposition of rectus femoris were assessed in this study, along with the protein levels of atrogin-1, p-PERK, Parkin, and COXIV. Results The wet weights and cross-sectional area decreased, and the fat deposition increased in rectus femoris after IM, along with the elevated protein levels of atrogin-1, p-PERK, Parkin, and decreased protein levels of COXIV. The above histomorphological and molecular changes can be partially ameliorated by electrical stimulation. Conclusions Immobilization of unilateral lower limb could induce rectus femoris atrophy, which can be partially rectified by electrical stimulation. PERK signal and Parkin-mediated mitophagy may be the mechanisms by which electrical stimulation can play a significant role.

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Effect of electrical muscle stimulation on the improvement of deltoid muscle atrophy in a rat shoulder immobilization model

Lee,

Kim

et al. 2024

Journal Orthopaedic Research

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Immobilization following trauma or surgery induces skeletal muscle atrophy, and improvement in the muscle atrophy is critical for successful clinical outcomes. The purpose of this study is to evaluate the effect of electrical muscle stimulation (EMS) on muscle atrophy. The study design is a controlled laboratory study. Eighty rats (56 to establish the deltoid muscle atrophy [DMA] model and 24 to evaluate the effect of EMS on the model) were used. DMA was induced by completely immobilizing the right shoulder of each rat by placing sutures between the scapula and humeral shaft, with the left shoulder as a control. After establishing the DMA model, rats were randomly assigned into three groups: low‐frequency EMS (L‐EMS, 10 Hz frequency), medium‐frequency EMS (M‐EMS, 50 Hz frequency), and control (eight rats per group). After 3 weeks, the deltoid muscles of each rat were harvested, alterations in gene expression and muscle cell size were evaluated, and immunohistochemical analysis was performed. DMA was most prominent 3 weeks after shoulder immobilization. Murf1 and Atrogin were significantly induced at the initial phase and gradually decreased at approximately 3 weeks; however, MyoD expressed an inverse relationship with Murf1 and Atrogin. IL6 expression was prominent at 1 week. The time point for the EMS effect evaluation was selected at 3 weeks, when the DMA was the most prominent with a change in relevant gene expression. The M‐EMS group cell size was significantly larger than that of L‐EMS and control group in both the immobilized and intact shoulders (all p < 0.05), without significant differences between the L‐EMS and control groups. The M‐EMS group showed significantly lower mRNA expressions of Murf1 and Atrogin and higher expressions of MyoD and Col1A1 than that of the control group (all p < 0.05). In immunohistochemical analysis, similar results were observed with lower Atrogin staining and higher MyoD and Col1A1 staining in the M‐EMS group. DMA model was established by complete shoulder immobilization, with the most prominent muscle atrophy observed at 3 weeks. M‐EMS improved DMA with changes in the expression of relevant genes. M‐EMS might be a solution for strengthening atrophied skeletal muscles and facilitating rehabilitation after trauma or surgery.

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Low-frequency electrical stimulation alleviates immobilization-evoked disuse muscle atrophy by repressing autophagy in skeletal muscle of rabbits

Cited by 7 publications

References 56 publications

Role of hypoxia-mediated pyroptosis in the development of extending knee joint contracture in rats

Role of hypoxia-mediated pyroptosis in the development of extending knee joint contracture in rats

Effect of Electrical Stimulation on Disuse Muscular Atrophy Induced by Immobilization

Effect of electrical muscle stimulation on the improvement of deltoid muscle atrophy in a rat shoulder immobilization model

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