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Orexin A expression and promoter methylation in patients with alcohol dependence comparing acute and protracted withdrawal

机译:酒精依赖患者急性和长期停药后Orexin A表达和启动子甲基化

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The orexins (hypocretins) are neuropeptides deriving from the lateral hypothalamus and may be of importance within the context of drug craving, withdrawal, and relapse. Therefore, the orexin A expression and promoter methylation in peripheral blood cells of 68 patients (41 male and 27 female patients at three different time points during withdrawal and 27 patients during stationary dehabituation therapy) suffering from alcohol dependence were assessed by quantitative reverse transcription-polymerase chain reaction and bisulfite sequencing. There was a statistically significant difference of orexin A expression between the three time points of withdrawal and long-term (LT) abstinence (F= 4.16, P= .011). This difference was most prominent in comparison with LT abstinence (t= -3.08, P= .0032). Expression was significantly associated with the severity of withdrawal symptoms measured with the Withdrawal Syndrome Scale for Alcohol and Related Psychoactive Drugs (WSA) (t= 2.17, P= .0356). The stronger the withdrawal symptoms, the lower the orexin A expression (F= 4.69, P= .036). Body mass index (t= 2.15, P= .041), the severity of withdrawal measured with the WSA (t= 2.595, P= .0133), craving measured either by the Obsessive Compulsive Drinking Scale (t= 2.77, P= .0085) or the Lübecker Craving Questionnaire (t= -2.23, P= .0314) had a significant influence on orexin A expression taking into account mean methylation of the CpG island of the orexin A promoter during withdrawal. Orexin A may be a possible candidate to further elucidate mechanisms of alcohol withdrawal taking into account energy homoeostasis in the circuit of reward and motivation.
机译:食欲素(hypocretins)是源自下丘脑外侧的神经肽,在渴望药物,戒断和复发的情况下可能很重要。因此,通过定量逆转录聚合酶评估了68名酒精依赖患者的戒酒过程中食欲素A的表达和启动子甲基化水平(分别在戒断期间三个不同时间点的男性41例和女性27例,以及在固定居所治疗中的27例)。链反应和亚硫酸氢盐测序。在退出的三个时间点和长期(LT)戒断之间,orexin A表达存在统计学上的显着差异(F = 4.16,P = .011)。与LT戒断相比,这种差异最为明显(t = -3.08,P = .0032)。表达与戒断症状的严重程度显着相关,戒断症状的严重程度与戒酒综合症状量表(WSA)相关(t = 2.17,P = .0356)。戒断症状越强,食欲素A表达越低(F = 4.69,P = .036)。体重指数(t = 2.15,P = .041),通过WSA测得的戒断严重程度(t = 2.595,P = .0133),通过强迫性饮酒量表(t = 2.77,P =)来衡量渴望。 0085)或Lübecker渴望调查表(t = -2.23,P = .0314)考虑到orexin A启动子的CpG岛在撤药过程中的平均甲基化,对orexin A的表达有重大影响。考虑到奖励和动机回路中的能量均等作用,食欲素A可能是进一步阐明酒精戒断机制的可能候选者。

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