The Effect And The Responding Mechanism Of Dexmedetomidine On Inflammatory Response In Rats With Sepsis

Objective To investigate the effect of dexmedetomidine (DEX) on inflammatory response and the impact on survival rate in rats with sepsis, and to explore the correlation between its responding mechanism and the cholinergic anti-inflammatory pathway.Methods40male Wistar rats were randomly divided into five groups:control group (group C), normal saline(NS) treatment group (group N), DEX treatment group (group D), α-bungarotoxin-tetramethylrhodamine(α-BGT)+DEX treatment group (group B) and α-BGT group (group A). Lipopolysaccharide (LPS) was injected to the vein to reproduce a classic sepsis model, while in control group,same volume of NS was used. Different treatment was given to the corresponding group, and then Venous blood was taken at time points. Behavioral changes and mortality rate of rats were recorded, and all survived rats were sacrificed48hours after LPS injection with their spleen taken. Detecting the content of the early inflammatory mediators such as Tumor necrosis factor-α (TNF-α), Interleukin-6(IL-6) and the late inflammatory mediators such as High-mobility group boxl protein (HMGB1) in blood serum and spleen by ELISA and WB, Histopathology changes in spleen tissue were observed with hematoxylin eosin (HE) stain, and a7nicotinic acetylcholine receptor (a7nAChR) expression with immunohistochemistry.Results Of the five groups, the mortality rate of rats,the serum level of TNF-a,IL-6and the content of secreting type of HMGB1in spleen all had statistical significance(all P<0.05), but no statistical significance were observed in the serum level of HMGB1and the expression of α7nAChR in these groups(all P>0.05). The results suggested that DEX could reduce the serum level of the early and the late inflammatory mediators, and also the content of secreting type of HMGB1in spleen in septic rats. The anti-inflammatory effect of DEX could be blocked by a-BGT, at least in part, so a7nAChR might be involved in the anti-inflammatory effect of DEX, however, the effect was not through the increase of a7nAChR in receptor expression.Conclution DEX has a certain anti-inflammatory effects of early and late in rats with sepsis,and can also reduce the mortality rate, which may be generated by activating the cholinergic anti-inflammatory pathway.8Figures,6Tables,48References.