酒精依赖大鼠前额叶皮质miRNAs差异表达及靶向调控分析  

The differential expressions and targeted regulation of miRNAs in the prefrontal cortex of rats with alcohol dependence

作　　者：辛凤[1] 闫丽娟 刘丽萍[1] 周鑫鑫 胡建[1] 

机构地区：[1]哈尔滨医科大学附属第一医院精神科,哈尔滨150000 [2]哈尔滨医科大学附属第四医院心理科,哈尔滨150000

出　　处：《中华行为医学与脑科学杂志》2017年第9期782-787,共6页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金项目（81271471）;黑龙江省卫生计生委科研课题项目（2012-519）

摘　　要：目的探讨酒精依赖与miRNAs表达之间的关系，以及miRNAs在酒精依赖病理过程中可能的的作用机制。方法用灌胃法制备酒精依赖大鼠模型，将造模成功的酒精依赖大鼠随机分为持续饮酒组与戒断组，用基因芯片检测酒精依赖持续饮酒组、戒断组和空白对照组各3只大鼠前额叶皮质脑区miRNAs的差异表达，利用分子生物学软件对差异表达的miRNAs的可能的靶基因进行分析。结果酒依赖持续饮酒组与对照组相比，miR-532—3p、miR-20b-3p、miR-411-3p、miR-16—3p、miR-299a-3p表达上调，miR-218b、miR-182、miR-122—5p、miR-1912—3p、miR-551b-3p表达下调。酒精依赖戒断组与对照组相比，miR-292—5p表达上调，miR-96—5p、miR-182、miR-144—5p表达下调。持续饮酒组与戒断组比较，miR-1298、miR-292—5p、miR-122—5p、miR-3065—5p、miR-55lb-3p表达上调，miR-382—3p、miR-55lb-5p表达下调。这些差异表达的miRNAs可能作用于NEGR1、CDC42、Bcl2、CACNA1C、BDNF、ALDH和IGF-1等基因，从而在酒精依赖的病理过程中发挥作用。结论miRNAs可能通过交互作用调控靶基因的表达，参与酒精依赖的发病过程。Objective To explore the relationship between alcohol dependence and miRNAs expression,and the possible mechanism of miRNAs in the process of alcohol dependence. Methods Alcohol dependence model rats were established by intragastric administration.The successful model rats of ethanol dependent were randomly divided into continuous alcohol group（ n= 3） and withdrawal group（ n= 3）.The expression of miRNAs in the the prefrontal cortex of rats were detected using gene chip in rats of continuous alcohol group, withdrawal group and normal control group. The target genes for miRNAs with differentially expressed were analyzed by bioinformatics methods. Results The results showed that the expression of miR- 532-3 p, miR-20b- 3p, miR-411-3p, miR-16-3p, miR-299a-3p was up-regulated, and the expression miR- 218b, miR- 182, miR-122-5p, miR-1912-3p, miR-551 b-3p was down-regulated in the continous drinking group compared with those in the control group.Compared with control group, miR-292-5p up-regulated expression and miR-96-5p, miR-182, miR-144-5p reduced expression in alcohol group. Compared with alcohol withdrawal group, miR -1298, miR-292-5p, miR -122-5p, miR-3065-5p, miR-55 lb-3p up-regulated expression and miR-382-3p,miR-551b-5p reduced expression in continued drinking group. These differentially expressed of miRNAs may targeted to NEGR1, CDC42, Bcl2, CACNA 1 C, BDNF, ALDH and IGF- 1 genes. Those played a role in the pathogenesis of alcohol dependence. Conclusion MiRNAs may regulate the expression of target genes through interaction and participate in the pathogenesis of alcohol dependence.

关 键 词：酒精依赖 前额叶皮质 MIRNA 靶基因 

分 类 号：R749.6[医药卫生—神经病学与精神病学]