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大麻依赖患者中 CB1 和 CB2 受体的表达和启动子甲基化。

CB1 and CB2 receptor expression and promoter methylation in patients with cannabis dependence.

机构信息

Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.

出版信息

Eur Addict Res. 2013;19(1):13-20. doi: 10.1159/000338642. Epub 2012 Aug 28.

DOI:10.1159/000338642
PMID:22948261
Abstract

CB1 and CB2 receptors are influenced via exogenous and endogenous cannabinoids. To date, little is known regarding changes in receptor expression and methylation in THC (tetrahydrocannabinol) dependence. Therefore, the CB1 and CB2 receptor mRNA expression levels and promoter methylation status in the peripheral blood cells of 77 subjects (36 with THC dependence, 21 cigarette smokers and 20 nonsmokers) were assessed by quantitative real-time PCR and methylation-specific PCR. There was a significant difference in CB1 receptor expression levels between the three groups (ANOVA, p < 0.001, d.f. = 2, F = 71.3). The mean promoter methylation (%) was significantly negatively correlated with CB1 receptor mRNA expression levels (Spearman's rho: r = -0.37; p = 0.002). Using a mixed general linear model, it was demonstrated that the CB1 mRNA expression (as the dependent variable) was associated with the satisfaction with life scale (SWLS) (r = 0.101; T = 2.8; p = 0.007), craving (as measured with the VAS; r = -0.023; T = -2.3; p = 0.023) and the WHO-Assist Subscale for Cannabis consumption (r = -0.068; T = -2.4; p = 0.02). CB1 receptor expression levels and methylation status appear to be altered in subjects with THC dependence.

摘要

CB1 和 CB2 受体受外源性和内源性大麻素的影响。迄今为止,关于 THC(四氢大麻酚)依赖中受体表达和甲基化的变化知之甚少。因此,通过定量实时 PCR 和甲基化特异性 PCR 评估了 77 名受试者(36 名 THC 依赖者、21 名吸烟者和 20 名不吸烟者)外周血细胞中的 CB1 和 CB2 受体 mRNA 表达水平和启动子甲基化状态。三组之间 CB1 受体表达水平存在显著差异(ANOVA,p < 0.001,d.f. = 2,F = 71.3)。平均启动子甲基化(%)与 CB1 受体 mRNA 表达水平呈显著负相关(Spearman 相关系数:r = -0.37;p = 0.002)。使用混合一般线性模型表明,CB1 mRNA 表达(作为因变量)与生活满意度量表(SWLS)(r = 0.101;T = 2.8;p = 0.007)、渴望(用 VAS 测量;r = -0.023;T = -2.3;p = 0.023)和世界卫生组织大麻消费辅助量表(r = -0.068;T = -2.4;p = 0.02)相关。CB1 受体表达水平和甲基化状态似乎在 THC 依赖者中发生改变。

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