Effect of dexmedetomidine on hippocampal neuronal apoptosis in endotoxemic rats

Abstract

Objective To evaluate the effect of dexmedetomidine on hippocampal neuronal apoptosis in endotoxemic rats. Methods Twenty-four pathogen-free male Sprague-Dawley rats, aged 6 weeks, weighing 200-250 g, were randomly divided into 3 groups(n=8 each)using a random number table: control group(group C), endotoxemia group(group E), and dexmedetomidine group(group D). Dexmedetomidine 50 μg/kg was injected intraperitoneally, and lipopolysaccharide 5 mg/kg was injected via the caudal vein 30 min later in group D. Normal saline 2 ml was injected intraperitoneally, and lipopolysaccharide 5 mg/kg was injected via the caudal vein 30 min later in group E. Normal saline 2 ml was injected intraperitoneally, and normal saline 2 ml was injected via the caudal vein 30 min later in group C. At 12 h after the model was successfully established, Morris water maze test was used to assess the cognitive function.The escape latency, swimming distance and frequency of crossing the original platform were recorded, and the swimming speed was calculated.The rats were then sacrificed, and hippocampi were harvest for determination of neuronal apoptosis(by TUNEL)and expression of glucose-regulated protein 78(GRP78), CAAT/enhancer-binding protein homologous protein(CHOP)and caspase-12(by immunohistochemistry). The apoptosis index(AI)was calculated. Results There was no significant difference in the swimming speed between the 3 groups(P>0.05). Compared with group C, the escape latency and swimming distance were significantly prolonged, the frequency of crossing the original platform was significantly decreased, and the AI was significantly increased, and the expression of GRP78, CHOP, and caspase-12 was significantly up-regulated in E and D groups(P<0.05). Compared with group E, the escape latency and swimming distance were significantly shortened, the frequency of crossing the original platform was significantly increased, and the AI was significantly decreased, and the expression of GRP78, CHOP, and caspase-12 was significantly down-regulated in group D(P<0.05). Conclusion Dexmedetomidine reduces cognitive dysfunction probably through reducing hippocampal neuronal apoptosis mediated by endoplasmic reticulum stress in endotoxemic rats. Key words: Dexmedetomidine; Endotoxemia; Apoptosis; Hippocampus; Neurons