Role of hippocampal histone acetylation in isoflurane-induced amnestic effect in mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of hippocampal histone acetylation in isoflurane-induced amnestic effect in mice.Methods Fifty-four male C57BL/6J mice,aged 8 weeks,weighing 18-22 g,were randomly divided into 3 groups (n =18 each) using a random number tablecontrol group (group C),isoflurane group (group ISO) and histone deacetylase inhibitor sodium butyrate group (group SB).Group C inhaled 35％ oxygen for 30 ain,and ISO and SB groups inhaled the mixture of 35 ％ oxygen and 0.4％ isoflurane for 30 min,and then the animals underwent contextual fear conditioning training.After the end of training,normal saline 6 ml/kg was intraperitoneally injected in C and ISO groups,while in group SB,sodium butyrate 1.2 g/kg was intraperitoneally injected.One hour after the end of training,3 mice were sacrificed randomly in each group and their hippocampi were immediately removed for determination of the expression of acetylated histone-H3 (Ac-H3) and Ac-H4 by Western blot.Twenty-four hours after the end of training,contextual fear conditioning test and open field test were conducted.The freezing time,total distance and time of staying at the central zone were recorded.Results Compared with group C,Ac-H3 and Ac-H4 expression was significantly down-regulated,and the percentage of freezing time during testing was decreased in group ISO (P ＜ 0.05).Compared with group ISO,Ac-H3 and Ac-H4 expression was significantly up-regulated,and the percentage of freezing time during testing was increased in group SB (P ＜ 0.05).There was no significant difference in the percentage of freezing time during training,total distance and time of staying in the central zone among the 3 groups (P ＞ 0.05).Conclusion Hippocampal histone acetylation is involved in the regulation of isoflurane-induced amnestic effect in mice.