Role and Mechanism of Silent Information Regulator2 in Remifentanil-Induced Incisional Hyperalgesia in Rats
Objective:To investigate the role and mechanism of silent information regulator 2(Sirt2)in remifentanil-induced inci-sional hyperalgesia in rats.Methods:18 SD rats were randomly divided into group Ⅰ(incision group,n=6),RI group(remifentanil+inci-sion group,n=6)and RI+Sirt2 overexpression group(remifentanil+incision+Sirt2 overexpression group,n=6).In Ⅰ group,the incisional pain model was made in the plantar of the rat,and the equal volume of normal saline was injected in the abdomen for 30 min.The RI group and the RI+Sirt2 overexpression group were injected with remifentanil for 30 min while the incisional pain model was made in the plantar of the foot.The RI+Sirt2 overexpression group was injected with Sirt2 overexpression lentivirus 1 week in advance at the spinal cord level.The mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)were measured at 24 h before remifen-tanil or normal saline infusion and 2 h,6 h,24 h and 48 h after the end of remifentanil or normal saline infusion.The rats were sacrificed after the behavior test and the L3-5 spinal cord segments were taken.The expression of Sirt2 was detected by Western blot.The activity of superoxide dismutase 2(SOD2)was determined by enzyme-linked immunosorbent assay(ELISA).The superoxide anion level and NADPH oxidase activity were determined by chemiluminescence.Results:The time effect(F=683.602,624.033,all P＜0.001)and group× time interaction effect(F=9.142,4.550,all P＜0.001)of MWT and TWL in each group were significant,indicating that MWT and TWL had a tendency to change with time and the effect of time factor was different with different groups,and the difference between groups was statistically significant(F=93.157,25.176,all P＜0.001).Compared with group Ⅰ,MWT decreased and TWL shortened at T1-4 in group RI(P＜0.05).In RI+Sirt2 overexpression group,MWT was decreased at T2 and T4 time points,and TWL was shortened at T2-4 time points(P＜0.05).Compared with RI group,RI+Sirt2 overexpression group had higher MWT at T3A time point and longer TWL at T2-4 time point(P＜0.05).There was significant difference in the expression of Sirt2 protein among the three groups(F=265.643,P＜0.001).Compared with group Ⅰ,the expression level of Sirt2 in spinal cord tissue of RI group and RI+Sirt2 overexpression group decreased at 48 h after operation(P＜0.05).Compared with RI group,the expression level of Sirt2 in spinal cord tissue of RI+Sirt2 overexpression group increased at 48 h after operation(P＜0.05).There were significant differences in SOD2 activity,NADPH oxidase activity and super-oxide anion expression in spinal cord tissue among the three groups(F=13.543,14.813,19.675,all P＜0.001).Compared with group Ⅰ,the activity of SOD2 in spinal cord tissue of RI group and RI+Sirt2 overexpression group decreased at 48 h after operation,while the activity of NADPH oxidase and the level of superoxide anion increased(P＜0.05).Compared with RI group,the activity of SOD2 in spinal cord tissue of RI+Sirt2 overexpression group increased at 48 h after operation,and the activity of NADPH oxidase and superoxide anion decreased(P＜0.05).Conclusion:Sirt2 is involved in remifentanil-induced hyperalgesia in rats with incisional pain by regulating oxidative stress.
Silent information regulator 2RemifentanilRatHyperalgesiaOxidative stress
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