Effect of hippocampal DNA methyltransferases in sevoflurane induced neonatal cognitive impairments / 临床麻醉学杂志

ABSTRACT

Objective To observe the effect of hippocampal DNA methyltransferases (DNMTs)on neonatal cognitive impairments induced by sevoflurance exposure.Methods Sixty-four 7-day old male Sprague-Dawley rats were randomly divided into the following four groups (n =1 6)control group (group C),sevoflurane group (group S),sevoflurane+NaCl group (group SN),and sevoflurane+5-AZA group (group SA).Sevoflurane animals received 3% sevoflurane plus 30% oxy-gen for 2 hours daily for 3 consecutive days,and rats in group C were placed into the same container, which contained 30% oxygen only.Animals in group SA were intracerebroventricularly injected with 5-AZA (1 mg/kg),while group SN same volume of NaCl one hour before sevoflurane exposure. Open field and Morris water maze were given the four weeks after anesthesia (n =8).Rats without any behavior tests from each group (n =8)were euthanized 4 weeks after the treatment and the hip-pocampus was harvested.Quantitative real-time PCR and Western blot were used to detect the mRNA and protein levels of DNMT1,DNMT3a and DNMT3b.Results In the open field test,no significant difference was observed in the distance travelled and the time spent in the center of the arena.Com-pared with the group C,group S showed an increase in the latency,decreased time spent in the target quadrant,and the mRNA and protein levels of DNMT3a and DNMT3b in the hippocampus were sig-nificantly increased (P < 0.05).Compared with the group SN,group SA showed a decrease in the la-tency,more time spent in the target quadrant,and the mRNA and protein levels of DNMT3a and DNMT3b in the hippocampus were decreased (P < 0.05).There was no significant difference in the expression of DNMT1 among the four groups.Conclusion Sevoflurane exposure induces neonatal cog-nitive impairments later in life,which was accompanied by the increased mRNA and protein levels of DNMT3a and DNMT3b in the hippocampus.By contrast,pretreatment of 5-AZA decreased hipp-ocampal DNMT3a and DNMT3b,and ameliorated cognitive impairments.These results suggest that DNMTs are involved in sevoflurane induced neonatal cognitive impairments.