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

Objective To observe the effect of dexmedetomidine on the inflammatory response and mortality in rats with sepsis,and to explore the relationship between the anti-inflammatory mechanism of dexmedetomidine and cholinergic anti-inflammatory pathway.Methods Forty male Sprague-Dawley rats weighing 260-300 g were divided into four groups using a random number table method: normal saline group(S group),sepsis model group(L group),and dexmedetomidine group(D group),dexmedetomidine + cholinesterase group(A group).Except for S group,all other groups were treated with intraperitoneal injection of lipopolysaccharide to construct a sepsis model and given appropriate treatment.S group was injected intraperitoneally with equal volume of normal saline.Blood of each group of rats was sampled at time to observe the general condition of the rats in each group within 24 hours and 5-day mortality was calculated.Lungs were collected after death of the rats,and the remaining alive rats were sacrificed for the harvest of lungs.The levels of tumor necrosis factor-α、 interleukin-6,、interleukin-1β、acetylcholine and high mobility group box 1 protein in serum were detected by enzyme-linked immunosorbent assay.The content of high mobility group box 1 protein in lung tissue was detected by Western blotting,while hematoxylin-eosin staining was used to observe the histopathological changes of lung tissue.Result There was no significant difference in body weight between the four groups(P>0.05);there was a significant difference in the 5-day mortality rate between the four groups(P<0.05);there was a significant difference in serum levels of tumor necrosis factor-α、interleukin-6、interleukin-1β and high mobility group box 1 protein in rats(P<0.05).Compared with S group,the serum acetylcholine level in L group was decreased,the difference was statistically significant(P<0.05);serum acetylcholine levels in group D and group L were significantly higher,the difference was statistically significant(P<0.05).Serum acetylcholine levels were significantly lower in group A compared with group D(P<0.05).There was a significant difference in the content of the high mobility group box 1 protein in the lungs of the four groups of rats(P<0.05).Compared with S group,the other three groups had more serious lung injury,and pathological damage of lung in group D was lighter than that in group L and group A.Conclusion Dexmedetomidine could significantly reduce inflammation response and mortality in rats with sepsis.The mechanism may be related to cholinergic anti-inflammatory pathways.