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组蛋白H4第5位赖氨酸的乙酰化与海洛因使用有关,而非成瘾。

H4K5 histone acetylation of is associated with heroin administration rather than addiction.

作者信息

Xu Limin, Hong Qingxiao, Chen Xiaoying, Xu Xuting, Liu Huifen, Zhou Wenhua, Duan Shiwei

机构信息

Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, P.R. China; Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou, Zhejiang 313000, P.R. China.

Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, P.R. China.

出版信息

Exp Ther Med. 2016 Sep;12(3):1929-1933. doi: 10.3892/etm.2016.3517. Epub 2016 Jul 13.

Abstract

Diacetylmorphine hydrochloride (heroin) addiction is a chronic relapsing brain disorder that is a heavy public health burden worldwide. Brm/SWI2-related gene-1 () is a tumor suppressor gene that can influence embryogenesis and the development of the cerebellum. The current study aimed to investigate the effect of histone H4 lysine 5 (H4K5) modifications on the gene in brain tissue of the ventral tegmental area (VTA) of heroin-addicted rats. A total of 21 male Sprague Dawley rats were raised in a standard manner and underwent heroin self-administration training. Rats were randomly divided into three equal groups: Group A, self-administered delivery of heroin; group B, yoked delivery of heroin; and group C, yoked delivery of saline. The VTA was harvested and subjected to chromatin immunoprecipitation (ChIP) analysis. Gene expression was evaluated by quantitative polymerase chain reaction. We calculated the recovery rate, which indicated the percentage of the total input recovered by ChIP. Our results showed that was less associated with H4K5 histone modification in the group of rats that underwent heroin self-administration than in the other two groups (A vs. B, P=0.031; A vs. C, P=0.067). The recovery fold changes of the self-administration group and the passive-administration group were significantly different from those of the group with yoked saline (A vs. C, P=0.013; B vs. C, P=0.009; A vs. B, P=0.731). The results of the current study demonstrated that H4K5 histone acetylation of in the VTA may be associated with heroin administration, but not addiction.

摘要

盐酸二乙酰吗啡(海洛因)成瘾是一种慢性复发性脑部疾病,在全球范围内是一项沉重的公共卫生负担。Brm/SWI2相关基因-1()是一种肿瘤抑制基因,可影响胚胎发育和小脑发育。本研究旨在探讨组蛋白H4赖氨酸5(H4K5)修饰对海洛因成瘾大鼠腹侧被盖区(VTA)脑组织中该基因的影响。总共21只雄性Sprague Dawley大鼠以标准方式饲养,并接受海洛因自我给药训练。大鼠被随机分为三组,每组数量相等:A组,自我给药海洛因;B组,配对给药海洛因;C组,配对给药生理盐水。采集VTA并进行染色质免疫沉淀(ChIP)分析。通过定量聚合酶链反应评估基因表达。我们计算了回收率,即ChIP回收的总输入量的百分比。我们的结果表明,与接受海洛因自我给药的大鼠组相比,其他两组中该基因与H4K5组蛋白修饰的相关性较小(A组与B组比较,P = 0.031;A组与C组比较,P = 0.067)。自我给药组和被动给药组的回收倍数变化与配对生理盐水组有显著差异(A组与C组比较,P = 0.013;B组与C组比较,P = 0.009;A组与B组比较,P = 0.731)。本研究结果表明,VTA中该基因的H4K5组蛋白乙酰化可能与海洛因给药有关,但与成瘾无关。

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