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Dexmedetomidine ameliorates muscle wasting and attenuates the alteration of hypothalamic neuropeptides and inflammation in endotoxemic rats.
- Source :
-
PloS one [PLoS One] 2017 Mar 30; Vol. 12 (3), pp. e0174894. Date of Electronic Publication: 2017 Mar 30 (Print Publication: 2017). - Publication Year :
- 2017
-
Abstract
- Dexmedetomidine is generally used for sedaton in critically ill, it could shorten duration of mechanical ventilation, ICU stay and lower basic metabolism. However, the exact mechanism of these positive effects remains unkown. Here we investigated the hypothesis that dexmedetomidine could ameliorate muscle wasting in endotoxemic rats and whether it was related to hypothalamic neuropeptides alteration and inflammation. Fourty-eight adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline, followed by 50 μg/kg dexmedetomidine or saline administration via the femoral vein catheter (infusion at 5 μg·kg-1·hr-1). Twenty-four hours after injection, hypothalamus tissues and skeletal muscle were obtained. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF-1) as well as 3-methylhistidine (3-MH) and tyrosine release. Hypothalamic inflammatory markers and neuropeptides expression were also detected in all four groups. Results showed that LPS administration led to significant increase in hypothalamic inflammation together with muscle wasting. Increased hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine and amphetamine-related transcript (CART) and neuropeptides Y (NPY) and decreased agouti-related protein (AgRP) were also observed. Meanwhile dexmedetomidine administration ameliorated muscle wasting, hypothalamic inflammation and modulated the alteration of neuropeptides, POMC, CART and AgRP, in endotoxemic rats. In conclusion, dexmedetomidine could alleviate muscle wasting in endotoxemic rats, and it could also attenuate the alteration of hypothalamic neuropeptides and reduce hypothalamic inflammation.
- Subjects :
- Agouti-Related Protein metabolism
Animals
Endotoxemia metabolism
Hypothalamus drug effects
Inflammation metabolism
Interleukin-1 metabolism
Male
Methylhistidines metabolism
Muscle, Skeletal metabolism
Muscular Atrophy drug therapy
Muscular Atrophy metabolism
Nerve Tissue Proteins metabolism
Neuropeptide Y metabolism
Pro-Opiomelanocortin metabolism
Rats
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha metabolism
Dexmedetomidine therapeutic use
Endotoxemia drug therapy
Hypothalamus metabolism
Inflammation drug therapy
Muscle, Skeletal drug effects
Muscle, Skeletal pathology
Neuropeptides metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 12
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 28358856
- Full Text :
- https://doi.org/10.1371/journal.pone.0174894