RESEARCH ARTICLE
Electrical Stimulation Improves Rat Muscle Dysfunction Caused by Chronic Intermittent Hypoxia-Hypercapnia via Regulation of miRNA-Related Signaling Pathways Lu-Lu Pan1,2☯, Jiang-Qiong Ke1☯, Cui-Cui Zhao3, Shi-Yuan Huang1, Jie Shen1, XianXun Jiang1, Xiao-Tong Wang1* 1 Center of Neurology and Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China, 2 Department of Rehabilitation, the Traditional Chinese Medical Hospital of Wenzhou City, Wenzhou, China, 3 Wenzhou Medical University, Wenzhou, China ☯ These authors contributed equally to this work. *
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Abstract OPEN ACCESS Citation: Pan L-L, Ke J-Q, Zhao C-C, Huang S-Y, Shen J, Jiang X-X, et al. (2016) Electrical Stimulation Improves Rat Muscle Dysfunction Caused by Chronic Intermittent Hypoxia-Hypercapnia via Regulation of miRNA-Related Signaling Pathways. PLoS ONE 11 (3): e0152525. doi:10.1371/journal.pone.0152525 Editor: Ashok Kumar, University of Louisville School of Medicine, UNITED STATES Received: January 14, 2016 Accepted: March 15, 2016 Published: March 29, 2016 Copyright: © 2016 Pan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This research was supported by the Medical Science Research Foundation of Zhejiang Province grant (No. Y2080503). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) patients is common. Neuromuscular Electrical Stimulation (NMES) is a powerful exercise training that may relieve muscle dysfunction in COPD. This study investigated whether electrical stimulation may have atypical adaptations via activation of miRNA related pathways in counteracting COPD muscle dysfunction. Forty-eight male Sprague-Dawley rats were randomly assigned to 3 groups. With the exception of the rats in the control group, the experimental rats were exposed to chronic intermittent hypoxia-hypercapnia (CIHH) (9*11%O2,5.5*6.5%CO2) for 2 or 4 weeks. Electrical stimulation was performed immediately after each CIHH session. Following assessment of the running capacity, biopsy samples were obtained from the gastrocnemius of the rats. The miR-1, miR-133a and miR-133b levels were measured, as well as their related proteins: phosphorylation of Akt (p-AKT), PGC-1alpha (PGC-1α), histone deacetylase 4 (HDAC4) and serum response factor (SRF). Myosin heavy chainⅡa (MHCⅡa) and myosin heavy chainⅡb (MHCⅡb) were also measured to assess fiber type changes. After 2 weeks, compared with the controls, only miR-1 and miR-133a were significantly increased (p
