title: Electrical Stimulation Improves Rat Muscle Dysfunction Caused by Chronic Intermittent Hypoxia-Hypercapnia via Regulation of miRNA-Related Signaling Pathways.
abstract: 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<0.05) in the exposure group. After 4 weeks, the exposure group exhibited a decreased running distance (p = 0.054) and MHCIIa-to-MHCIIb shift (p<0.05). PGC-1α (p = 0.051), nuclear HDAC4 (p = 0.058), HDAC4, p-AKT, PGC-1α and SRF was also significantly decreased (p<0.05). In contrast, miR-1 and miR-133a were significantly increased (p<0.05). Four weeks of electrical stimulation can partly reversed those changes, and miR-133b exhibited a transient increase after 2 weeks electrical stimulation. Our study indicate miRNAs may have roles in the response of CIHH-impaired muscle to changes during electrical stimulation.
authors.affiliation: Center of Neurology and Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Department of Rehabilitation, the Traditional Chinese Medical Hospital of Wenzhou City, Wenzhou, China.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Pan
authors.affiliation: Center of Neurology and Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Jiang-Qiong
authors.initials: JQ
authors.lastname: Ke
authors.affiliation: Wenzhou Medical University, Wenzhou, China.
authors.forename: Cui-Cui
authors.initials: CC
authors.lastname: Zhao
authors.affiliation: Center of Neurology and Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Shi-Yuan
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Center of Neurology and Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Center of Neurology and Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Xian-Xun
authors.initials: XX
authors.lastname: Jiang
authors.affiliation: Center of Neurology and Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Wang
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002908:Chronic Disease; D004558:Electric Stimulation; D005786:Gene Expression Regulation; D006935:Hypercapnia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D010807:Physical Endurance; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012420:Running; D026362:Serum Response Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D026362:Serum Response Factor; D014157:Transcription Factors; D051057:Proto-Oncogene Proteins c-akt; D018995:Myosin Heavy Chains