ABSTRACT
Objective To investigate the effect of melatonin on isoflurane anesthesia-induced cognitive dysfunction in aged rats.Methods Seventy-five male SD rats,aged 18-20 months,weighing 350-400 g,were randomly assigned into 5 groups(n =15 each):control group(group C),1.5％ isoflurane group(group Ⅰ),melatonin 5 mg/kg group(group M1),melatonin 10 mg/kg group(group M2)and melatonin 20 mg/kg group(group M3).Group G inhaled a gas mixture of oxygen and air for4 h and group 1 inhsled 1.5％ isoflurane for4 h.Melatonin 5,10 and 20 mg/kg(in normal saline containing 1％ DMSO)were injected intrsperitoneally at 15 min before anesthesia and 3 h after the beginning of anesthesia in groups M1,M2 and M3 respectively,and then the animals inhaled 1.5％ isoflurane for 4 h.At the end of anesthesia,5 rats in each group were chosen and blood samples were taken to perform arterial blood gas analysis and to detect the blood glucose level and expression of phosphorylated Tau(p-Tau)protein in hippocampus.Ten rats in each group were chosen at 14 d after the end of anesthesia and Morris water maze was performed 3 times a day for 5 consecutive days to assess the cognitive function.Then the animals were sacrificed and hippocampi were removed for detection of p-Tau expression by Western blot.Results There were no significant differences in the parameters of arterial blood gas analysis and blood glucose level among the 5 groups(P ＞ 0.05).Compared with group C,the escape latency at 3-5 d was significantly prolonged,the probe time was significantly shortened,and the expression of p-Tau protein was up-regulated in groups I and M1(P ＜0.05),and no significant change was found in the indexes mentioned above in groups M2 and M3 (P ＞0.05).Compared with groups 1 and M1,the escape latency at 2-5 d was significantly shortened,the probe lime was significantly prolonged,and the expression of p-Tau protein was down-regulated in groups M2 and M3 (P ＜ 0.05).There were no significant differences in the indexes mentioned above between groups I and M1,and between groups M2 and M3(P ＞ 0.05).Conclusion Melatonin(10 and 20 mg/kg)can improve isoflurane anesthesia-induced cognitive dysfunclion in aged rats,which nay be related to inhibition of hyperphosphorylation of Tau protein in hippocampus.
