title: Dexmedetomidine ameliorates muscle wasting and attenuates the alteration of hypothalamic neuropeptides and inflammation in endotoxemic rats.
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.
authors.affiliation: Medical School of Nanjing University,Nanjing, Jiangsu, P.R China.
authors.forename: Minhua
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Medical School of Nanjing University,Nanjing, Jiangsu, P.R China.|Institute of General Surgery Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, P.R China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gao
authors.affiliation: Institute of General Surgery Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, P.R China.
authors.forename: Fengchan
authors.initials: F
authors.lastname: Xi
authors.affiliation: Medical School of Nanjing University,Nanjing, Jiangsu, P.R China.
authors.forename: Chun
authors.initials: C
authors.lastname: Cao
authors.affiliation: Medical School of Nanjing University,Nanjing, Jiangsu, P.R China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Medical School of Nanjing University,Nanjing, Jiangsu, P.R China.
authors.forename: Chenyan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Institute of General Surgery Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, P.R China.
authors.forename: Qiurong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Medical School of Nanjing University,Nanjing, Jiangsu, P.R China.|Institute of General Surgery Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, P.R China.
authors.forename: Wenkui
authors.identifier: http://orcid.org/0000-0002-2636-9207
authors.initials: W
authors.lastname: Yu
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D020927:Dexmedetomidine / Q000627:therapeutic use*; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D008762:Methylhistidines / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000188:drug therapy / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D054369:Agouti-Related Protein; D007375:Interleukin-1; D008762:Methylhistidines; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D014409:Tumor Necrosis Factor-alpha; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D011333:Pro-Opiomelanocortin; D020927:Dexmedetomidine; C028118:3-methylhistidine