The Role Of Iron Metabolism Disorders In Cognitive Dysfunction Induced By Sevoflurane And Isoflurane In Mice

Objective: To evaluate the role of iron metabolism disorders in cognitive dysfunction induced by sevoflurane and isoflurane in mice.Methods: Twenty-four healthy male Kunming mice,aged 12 months,weighing 45~55 g,were randomly divided into 3 groups(n=8 each)using a random number table: control group(group Con),sevoflurane group(group Sev)and isoflurane group(group Iso).The mice inhaled 2% sevoflurane in100% oxygen for 6 h in group Sev;The mice inhaled 1.4% isoflurane in 100%oxygen for 6 h in group Iso.The mice inhaled 100% oxygen for 6 h in group Con.Morris Water maze navigation experiment was carried out before anesthesia,which was lasted 5 days,4 times a day.It was performed again following 12 hours after anesthesia.The movement trajectory,escape latency and total distance were recorded with the camera and computer.Each mice was anesthetized with 0.4% pentobarbital sodium(1ml/100g)through intraperitoneal injection,chest was opened to expose the heart,normal saline was used to perfuse blood,then the head was cut off,brain was removed and cortex and hippocampus were separated from it.The expression of TfR1,ferrtin,FPN1 and DMT1(+IRE)proteins related to iron metabolism and phosphorylated Tau protein were detected by Western blot.Protein bands were obtained with chemiluminescence imaging system.The integrated optical density values for each protein band were then analyzed by using Image-Pro Plus 6.0 software.The ratio of integrated optical density of the target protein bands to the integrated optical density of the internal control protein bands reflected the expression level of the target proteins.SPSS13.0 software was used for statistical analysis,the above measurement data presenting normal distribution were described as mean±standard deviation(?).Comparison among groups was analyzed by using one-way ANOVA,and a P value<0.05 was considered statistically significant.Results:1 The results of Morris water maze test: there were no significant differences among three groups in the total distance and escape latency among three groups(P > 0.05).Compared with group Con,the total distance and escape latency were significantly extended in group Sev and group Iso(P<0.05).2 The expression levels of iron metabolism related proteins: compared with group Con,the expressions of Ferritin-L,Ferritin-H and FPN1 in cerebral cortex and hippocampus regions were significantly up-regulated,the expression of TfR1 was significantly down-regulated in Sev group(P<0.05),and the expression of DMT1(+IRE)was no significant change(P > 0.05).Compared with group Con,the expressions of ferritin-L,ferritin-H,FPN1,TfR1 and DMT1(+IRE)in cerebral cortex and hippocampus regions were no significant differences in Iso group(P>0.05).3 The expression level of phosphorylated tau protein: compared with group Con,the expression of phosphorylated Tau protein in cerebral cortex and hippocampus regions was significantly up-regulated in group Sev and group Iso(P<0.05).Conclusion: The mechanism by which sevoflurane results in cognitive dysfunction in mice may be related to cerebral iron metabolism disorders.Cerebral iron metabolism disorders doesn't occur in the process that isoflurane induces cognitive dysfunction in mice.