ABSTRACT
Objective Constant light exposure can lead to hypercatabolism. The aim of this study was to investigate the effects of different light rhythm on skeletal muscle metabolism in endotoxemia rats, and looked for the optimal light rhythm that could reduce skeletal muscle consumption and enhance the recovery of patients with sepsis. Methods 54 adult male S-D rats were randomly divided into 3 groups on average：Control group (intraperitoneal injection of normal saline +12h/12h light-dark cycle for 7 days), LPS- regular light group (intraperitoneal injection of lipopolysaccharide(LPS) +12h/12h light-dark cycle for 7 days) and LPS-constant light group (intraperitoneal injection of LPS + constant light for 7 days). All experimental animals were sacrificed on the 8th day. The level of skeletal muscle metabolites 3-methylhistidine (3-mh) and tyrosine, atrophy genes MAFbx and murf-1 mRNA and hypothalamic clock genes BMAL1, CLOCK and neuropeptide POMC were also detected. Results The food intake, weight growth ratio and the ratio of extensor digitorum longus/weight in the LPS-constant light group were significantly lower than those in the LPS-regular light group (P <0.05), and both groups were significantly lower than those in the control group (P <0.01). The skeletal muscle metabolites 3-methylhistidine(nmol/g) and tyrosine(nmol/g) in the LPS-constant light group rats (6.200±0.273 and 461.039±13.292) were significantly higher than those in the LPS- regular light group (5.197±0.263 and 375.744±20.308) and the control group (3.244±0.275 and 290.935±19.065,all P <0.05). The expression levels of atrophic genes MAFbx and murf-1 mRNA and tnf-alpha and il-1 mRNA in hypothalamus in the LPS-constant light group were significantly higher than those in the LPS- regular light group(P <0.05), and both groups were significantly higher than those in the control group (P <0.05). The expression of the clock genes(BMAL1 and CLOCK) in the showed obvious rhythm (SE (A) /A<0.3) in the LPS-regular light group and the control group. The expression of BMAL1 was highest at the beginning of the illumination period, while the expression of CLOCK was high during the illumination period and decreased during the darkness period. In the LPS-constant light group, the expression of BMAL1 and CLOCK rhythm lost rhythm. Conclusion Normal light rhythm can maintain the normal rhythm expression of hypothalamic clock gene in rats with endotoxemia and reduce POMC-mediated skeletal muscle consumption, which may be of positive significance for the enhanced recovery of sepsis.
ABSTRACT
Objective Sepsis is often accompanied by serious disorder of energy metabolism, which is characterized by high catabolism, leading to irreversible acute skeletal muscle decomposition. As a new sedative, dexmedetomidine can alleviate the hypercatabolism of sepsis to a certain extent, so it has the potential to improve acute skeletal muscle decomposition. The present work aims to investigate the effects of dexmedetomidine on the expressions of hypothalamus neuropeptides and skeletal muscle atrophy gene in endotoxemic rats.Methods Thirty-six male Sprague Dawley rats were randomly divided into three groups (n=12): control group(group CON),-model group(group LPS-CON) and intervention group(group LPS-DEX). The endotoxemic rat model was established by injecting lipopolysaccharide (LPS) intraperitoneally. After 24 hours intervention, the expressions of hypothalamic neuropeptide (POMC, CART, AgRP and NPY) mRNA as well as MuRF-1 and MAFbx mRNA in skeletal muscle in rats were detected by RT-PCR.Results Compared with control group, the expressions of POMC, CART, MuRF-1 and MAFbx mRNA were significantly up-regulated (P＜0.05), while the expression of AgRP mRNA was significantly down-regulated in-model group (P＜0.05). Compared with-model group, the expressions of POMC, CART, MuRF-1 and MAFbx mRNA were significantly down-regulated (P＜0.05), while the expression of AgRP mRNA was significantly up-regulated in intervention group (P＜0.05).Conclusion Dexmedetomidine could regulate the expressions of hypothalamus neuropeptides and skeletal muscle atrophy gene in endotoxemic rats.