Effect of histone lysine methtyltransferase G9a in sevoflurane-induced long-term cognitive impairments in the developing brain of neonatal rats / 临床麻醉学杂志

ABSTRACT

Objective To investigate the role of histone lysine methyltransferase G9a in sevoflurane-induced cognitive impairment in the developing brain of neonatal rats.Methods Thirty-six 5-day-old male SD rats were randomly divided into 3 groups (n =12)control group,sevoflurane group and Bix01294 (the inhibitor of histone lysine methyltransferase G9a)group.The rats in the sevoflurane group and the Bix01294 group received 3% sevoflurane anesthesia for 2 hours once a day at postnatal 5-7 days (P5-P7 ).The rats in the Bix01294 group received Bix01294 (10 mg/kg)subcu-taneously at 1 5 min before anesthesia,and the rats in the control group and sevoflurane group received normal saline for injection (0.1 ml)at the same time.The open-field test and fear condition-ing test were performed at P3 5 and P3 9-P41 ,respectively.The tissues of hippocampus were collected at P42 to measure the levels of G9a,histone H3 lysine 9 dimethylation (H3K9me 2 )and synapsin 1. Results Compared with the control group,the percentage of freezing time of sevoflurane group was significantly decreased in the contextual fear condition test,while the levels of G9a and H3K9me 2 were significantly increased and the level of synapsin 1 was significantly decreased (P <0.01).How-ever,the percentage of freezing time of Bix01294 group was significantly increased,while the levels of G9a and H3K9me 2 were significantly decreased and the level of synapsin 1 was significantly in-creased compared with the sevoflurane group (P <0.05).There was no difference in the total distance and residence time in the central grid in the open-field test,and the percentage of freezing time in the cued fear condition test among the three groups.Conclusion Histone lysine methyltransferase G9a is involved in the sevoflurane-induced long-term cognitive impairment in developing brain of neonatal rats,which may be associated with the increase of H3K9me 2 and the down-regulation of synapsin 1 in the hippocampus.