Effect of dexmedetomidine on inflammatory responses in brain tissues in septic rats

Objective To evaluate the effect of dexmedetomidine on the inflammatory responses in brain tissues in septic rats.Methods Seventy-two male Sprague-Dawley rats,aged 10 weeks,weighing 250-280 g,were randomly divided into 4 groups (n =18 each):control group (group C); sepsis group (group lipopolysaccharide (LPS)) ; distilled water group (group DW) and dexmedetomidine group (group D).Sepsis was induced by intraperitoneal injection of LPS 5 mg/kg (dissolved in normal saline 1 ml) in groups LPS,DW and DEX,while normal saline 1 ml was injected intraperitoneally in group C.Distilled water 20 μl was injected into the lateral cerebral ventricle in group DW,while dexmedetomidine 3 μg/kg (dissolved in distilled water 20μl) was injected into the lateral cerebral ventricle in group DEX.Six animals were sacrificed at 1,2 and 6 h after administration and hippocampi were removed for determination of TNF-α and IL-6 contents (by ELISA) and TLR4 mRNA expression in hippocampal tissues (by RT-PCR).Results Compared with group C,TNF-α and IL-6 contents in hippocampus tissues were significantly increased at each time point after administration in group LPS (P ＜ 0.05).Compared with group LPS,no significant change was found in TNF-α and IL-6 contents in hippocampal tissues (P ＞ 0.05),and TLR4 mRNA expression was significantly up-regulated at each time point after administration in group DW (P ＜ 0.05).Compared with group DW,TNF-α and IL-6 contents in hippocampal tissues were significantly decreased at each time point after administration,and TLR4 mRNA expression was significantly up-regulated at 2 and 6 h after administration in group DEX (P ＜ 0.05).Conclusion Dexmedetomidine can reduce inflammatory responses in brain tissues in septic rats via down-regulating TLR-4 mRNA expression. Key words: Dexmedetomidine ;  Sepsis ;  Inflammation