大鼠内侧前额叶皮质5-氮杂-2’-脱氧胞苷对酒精滥用的调控作用  

Regulation of 5-aza-2′-deoxycytidine in the Medial Prefrontal Cortex of Rats on Alcohol Abuse

作　　者：唐华 赵曙光 窦维佳 赵丽 张哲 赵保民 王景杰 党伟[2] TANG Hua;ZHAO Shuguang;DOU Weijia;ZHAO Li;ZHANG Zhe;ZHAO Baomin;WANG Jingjie;DANG Wei(Tangdu Hospital of the Military Medical University of the Air Force,Xi＇an 710038;Xi＇an Mental Health Center,Xi＇an 710038)

机构地区：[1]空军军医大学唐都医院,西安710038 [2]西安市精神卫生中心,西安710038

出　　处：《宁夏医科大学学报》2018年第7期752-757,共6页Journal of Ningxia Medical University

基　　金：陕西省重点研发计划(2017SF-244);2017年西安市和计划生育委员会卫生科研人才项目(J201202024)

摘　　要：目的探索DNA甲基转移酶(DNA methyltransferases,DNMTs)的抑制剂5-氮杂-2'-脱氧胞苷(5-Aza-2'-deoxycytidine,5-Aza-dc)对酒精滥用的调控作用。方法建立大鼠慢性酒精暴露模型,将5-Aza-dc双边注射至大鼠内侧前额叶皮质(medial prefrontal cortex,mPFC),通过双瓶选择实验检测大鼠饮酒情况,通过旷场实验检测大鼠自主活动量和焦虑样行为;Western blot定量检测mPFC组织中DNMT1、DNMT3A和DNMT3B蛋白的表达。结果 5-Aza-dc可以降低饮酒组大鼠的饮酒量和酒精偏爱率(P<0.01);5-Aza-dc可加强饮酒组大鼠的焦虑样行为(P <0.05)。同时,5-Aza-dc逆转了酒精诱导的DNMT3A和DNMT3B的高表达(P<0.05)。酒精不影响DNMT1的表达,5-Aza-dc可降低DNMT1的表达(P<0.01)。结论 5-Aza-dc可减少大鼠的饮酒量,并不影响大鼠的自主活动量。Objective To explore the role of 5-Aza-2＇-deoxycytidine（5-Aza-dc）,an inhibitor of DNA methyl-transferases（DNMTs）in alcohol abuse. Methods Rat chronic alcohol exposure model was established by bilateral injection of 5-Aza-dc into medial prefrontal cortex（m PFC）,alcohol consumption was detected by double bottle selection test,autonomic activity and anxiety-like behavior were detected by open field test,and DNMT1,DNMT3 A and DNMT3 B were quantitatively detected by Western blot. Results 5-Aza-dc could decrease the alcohol intake and alcohol preference rate（P〈0.01）,strengthen the anxiety-like behavior（P〈0.05）.Meanwhile,5-Aza-dc reversed the high expression of alcohol induced DNMT3 A and DNMT3 B（P〈0.05）.Alcohol did not affect the expression of DNMT1,and 5-Aza-dc reduced the expression of DNMT1（P〈0.01）.Conclusion 5-Aza-dc can significantly reduce alcohol intake in rats and does not affect the locomotor activity.

关 键 词：酒精滥用 内侧前额叶皮质 5-AZA-DC DNA甲基转移酶 

分 类 号：R394.3[医药卫生—医学遗传学]