海马组蛋白乙酰化修饰在异氟醚致小鼠遗忘效应中的作用  

Role of hippocampal histone acetylation in isoflurane-induced anmestic effect in mice

作　　者：卿秋菊 钟涛[1] 张艳峰[1] 刘心瑶[1] 鄢建勤[1] 

机构地区：[1]中南大学湘雅医院麻醉科,长沙市410008

出　　处：《中华麻醉学杂志》2013年第11期1346-1348,共3页Chinese Journal of Anesthesiology

基　　金：湖南省自然科学基金（12JJ5051）

摘　　要：目的评价海马组蛋白乙酰化修饰在异氟醚致小鼠遗忘效应中的作用。方法SPF级雄性C57BL／6J小鼠54只，8周龄，体重18～22g，采用随机数字表法，将其分为3组（n=18）：对照组（c组）、异氟醚组（ISO组）和组蛋白去乙酰化酶抑制剂丁酸钠组（sB组）。c组吸入35％氧气30min，ISO组和sB组吸入35％氧气和O．4％异氟醚的混合气体30min，然后进行条件恐惧训练。训练结束后，c组和ISO组腹腔注射生理盐水6ml／kg，SB组腹腔注射丁酸钠1．2g／kg。于条件恐惧训练结束后1h时，各组随机处死6只小鼠，取海马组织，采用Westernblot法测定乙酰化组蛋白H3（Ac-H3）Ac-H4的表达。余小鼠于条件恐惧训练后24h时，进行条件恐惧测试和旷场实验，记录凝滞时间、总路程和中央区停留时问。结果与c组比较，ISO组海马Ac-H3和Ac-H4的表达下调，测试阶段凝滞时间百分比降低（P〈0．05）；与ISO组比较，sB组海马Ac-H3和Ac-H4的表达上调，测试阶段凝滞时间百分比升高（P〈0．05）；3组间训练阶段凝滞时问百分比、总路程和中央区停留时间比较差异无统计学意义（P〉0．05）。结论海马组蛋白乙酰化修饰参与调控异氟醚致小鼠的遗忘效应。Objective To evaluate the role of hippocampal histone acetylation in isoflurane-induced am- nestic 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 table： control group （group C）, isoflurane group （group ISO） and histone deacetylase inhibitor sodium butyrate group （group SB）. Group C inhaled 35 % oxygen for 30 rain, 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 aeetylated 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 Com- pared with group C, At-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 Ae-H4 ex- pression was significantly upTregulated, 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 dis- tance and time of staying in the central zone among the 3 groups （ P 〉 0.05 ）. Conclusion Hippoeampal histone acetylation is involved in the regulation of isoflurane-indueed amnestic effect in mice.

关 键 词：异氟醚 遗忘 乙酰化作用 组蛋白类 

分 类 号：R614[医药卫生—麻醉学]