亲代Wistar大鼠慢性酒精暴露对子代htr3a组蛋白修饰和酒精觅药行为的影响  

The effect of chronic ethanol exposured parental Wistar rats on the histone modification in htr3a and the ethanol-seeking behavior of the offspring

作　　者：徐亚辉[1] 王传升[1] 刘铁桥[2] 郝伟[2] 张瑞岭[1] 

机构地区：[1]河南省精神病医院成瘾科,新乡453002 [2]中南大学湘雅二医院精神卫生研究所

出　　处：《中华精神科杂志》2014年第2期103-108,共6页Chinese Journal of Psychiatry

基　　金：国家自然科学基金（30971050）;河南省科技创新人才计划（094200510005）

摘　　要：目的 了解亲代酒精暴露诱导的组蛋白修饰改变是否遗传给子代,探讨亲代酒精暴露对子代的酒精觅药行为影响的表观遗传机制.方法 24只雄性和24只雌性Wistar大鼠按照完全随机法随机予以酒精或生理盐水处理15 d,后戒断15 d,两两配对成4个组,繁殖后取其子代分为2组：子代非酒精暴露组（48只）,子代酒精暴露组（48只）.采用条件性位置偏爱（CPP）模型评价子代的酒精觅药行为.实时荧光定量逆转录-聚合酶链反应（RT-PCR）和染色质免疫共沉淀（CHIP）方法检测亲代和子代慢性酒精暴露的Wistar大鼠前额叶皮质（PFC） htr3a mRNA水平和启动子区组蛋白修饰情况.结果 （1）子代非酒精暴露组：亲代酒精处理组的子代htr3a mRNA水平、htr3a基因启动子区组蛋白H3K9乙酰化水平比亲代生理盐水处理组的子代升高（F=31.496,P＜0.001;F=10.333,P＜0.001）.（2）子代酒精暴露组：亲代酒精处理组的子代CPP分值比亲代生理盐水处理组的子代升高（F =11.436,P＜0.001）;其htr3a mRNA水平、htr3a基因启动子区组蛋白H3K9乙酰化水平比亲代生理盐水处理组的子代升高（F=26.105,P＜0.001;F=3.740,P＜0.05）.结论 亲代慢性酒精暴露引起的组蛋白H3K9乙酰化可稳定地遗传给子代,亲代慢性酒精暴露可能通过增加子代htr3a基因启动子区组蛋白H3K9乙酰化增强子代的酒精觅药行为.Objective To investigate whether the offspring of chronic ethanol exposured Wistar rats inherited the changes of histone modification. To explore the epigenetic mechanism of the effect of chronic ethanol exposured Wistar rats on the ethanol-seeking behavior of their offspring. Methods Twenty-four male and 24 female adult Wistar rats were randomly injected ethanol and saline for 15 days and experienced withdrawal for 15 days, then coupled into 4 groups. The offspring of the 4 groups were divided into two groups, 48 rats without ethanol exposure and 48 rats with ethanol exposure. Conditioned place preference （CPP） was used to evaluate the ethanol-seeking behavior. Using reverse transcription-polymerase chain reaction （RT-PCR） and chromatin immunopreeipitation （CHIP） assays, the levels of htr3a mRNA and specific histone modifications in htr3a promoter region of prefrontal cortex （PFC） were determined respectively. Results （ 1 ） In the offspring without ethanol exposure, the htr3a mRNA expression level and the H3K9 acetylation in htr3a promoter region were significantly increased in ones with parental ethanol exposured than ones with parental saline exposured （ F = 31. 496, P 〈 0. 001 ; F = 10. 333, P 〈 0. 001 ）. （2） In the offspring with ethanol exposure, the CPP score was significantly higher in ones with parental ethanol exposured than ones with parental saline exposured （ F = 11. 436, P 〈 0. 001 ）. The htr3a mRNA expression level and the H3K9 aeetylation in htr3a promoter region were significantly higher in offspring of saline exposured rats than ones of ethanol exposured rats （ F = 26. 105, P 〈 0. 001 ; F = 3. 740, P 〈 0. 05 ）. Conclusion Chronic ethanol exposure could induce H3K9 aeetylation in htr3a promoter region and be inherited between generations. Parental exposure to ethanol may enhance the ethanol-seeking behavior through mechanisms involving H3K9 acetylation in htr3a promoter region.

关 键 词：组蛋白类 酒精相关性障碍 htr3a基因 WISTAR大鼠 

分 类 号：R749.62[医药卫生—神经病学与精神病学]