Effect Of Dexmedetomidine Pretreatment On Hippocampus Nogo-A Expression And Cognitive Function In Sepsis Rats

Objective:Sepsis is a systemic inflammatory response(SIRS)caused by the presence of various microorganisms or toxins in the human body.Over the past decade,the incidence of sepsis has increased dramatically.With the improvement of medical level,the mortality rate has been greatly reduced,but the incidence of cognitive impairment in cured patients has increased significantly.Clinical studies have shown that the incidence of cognitive impairment in sepsis patients during hospitalization is as high as 60%,including changes in learning,memory,Association and other aspects.Cognitive impairment seriously affects the quality of life of patients,so the study of cognitive impairment caused by sepsis is of great significance.Studies have shown that neuronal necrosis and apoptosis in hippocampus may be the main cause of neurological impairment and learning and memory impairment.At present,the difficulty of nerve regeneration is mainly related to the inhibiting factors in the microenvironment of the central nervous system,including Nogo protein,myelin-associated glycoprotein(MAG),oligodendrocyte myelin glycoprotein(OMGP),which are all related to Nogo receptor.(nogo receptor,NgR)can inhibit axon regeneration of mature neurons and induce cell growth cone collapse,thus inhibiting the repair of nervous system damage.Among them,the inhibition of Nogo protein is the most obvious,and NgR may be the common point of action of various axon growth inhibitory proteins.Therefore,this experiment established sepsis rat model by intraperitoneal injection of lipopolysaccharide to observe the changes of behavioral patterns,verify the changes of related indicators of inhibition of axon regeneration in nervous system microenvironment,and lay the foundation of experimental research for finding ways to prevent or treat sepsis.Methods: A total of twenty-four pathogen-free male SD rats,aged 6 weeks,weighing200-250 g,were divided into 4 groups(n=6 each)using a random number table:control group(group C),LPS group(group L),DEX plus LPS group(group D+L)and DEX only group(group D).Group C received no treatment.DEX 50 ? g/kg wasinjected intraperitoneally and LPS 5 mg/kg was injected via caudual vein in 15 min later in group DEX+LPS.Normal saline 1ml was injected intraperitoneally and LPS 5mg/kg was injected via caudal vein 15 min later in group LPS.DEX 50?g/kg was injected intraperitoneally in group DEX.Morris water maze test were performed 48 h after administration to estimate the cognitive function.After the behavioral tests,the animals were sacrificed,and their hippocampus were removed to detect the expression of protein Nogo-A by method of immunohistochemistry and Western blot.Results: Compared with group C and D,the escape latency and swimming distance were prolonged and numbers of crossing the platform were decreased in group L and D+L(p<0.05);Compared with group L,the escape latency and swimming distance were shortened and numbers of crossing the platform were increased in group D+L(p < 0.05).Compared with group C and D,the expression of Nogo-A were up regulated in group L and D+L(p < 0.05);Compared with group L,the Nogo-A expression was down regulated of group D+L,IOD value decreased significantly(p<0.05).Conclusion: The mechanism by which DEX at tenuating cognitive dysfunction induce by sepsis may be related to the down regulation of Nogo-A in hippocampus of rats.