Larson Scott J, Putnam Elizabeth A, Schwanke Corbin M, Pershouse Mark A
Armed Forces Institute of Pathology, Washington, DC, USA.
J Anal Toxicol. 2007 Jan-Feb;31(1):15-22. doi: 10.1093/jat/31.1.15.
The exogenous administration of gamma-hydroxybutyrate (GHB) as a drug of abuse, and especially in date rape sexual assaults, has recently increased. Chromatographic techniques are used to detect GHB in blood or urine, with a window of detection limited to 12 h. This brief window makes the proof of administration problematic in most rape cases. This study is aimed to extend the window of detection through surrogate markers of GHB administration. Microarray technology is used in a DBA/2J mouse model to detect gene expression changes in peripheral blood after GHB exposure at times as long as 96 h post exposure. This study focuses on two of the most significantly altered transcripts, epiregulin and phosphoprotein enriched in astrocytes 15 (Pea-15). Both genes have increased the ribonucleic acid expression (8.5- and 4.6-fold upregulation at 96 h, respectively) in GHB-dosed mice (1 g/kg) as compared with the control. To confirm these results at the protein level, an intracellular flow cytometric assay is developed to detect protein level changes in the peripheral blood of both these potential biomarkers after GHB exposure. These results suggest that after further development, epiregulin and Pea-15 may prove to be significant surrogate markers in the indirect detection of GHB administration.
作为一种滥用药物，尤其是在约会强奸性侵犯中，γ-羟基丁酸（GHB）的外源给药最近有所增加。色谱技术用于检测血液或尿液中的GHB，检测窗口期限于12小时。这个短暂的窗口期使得在大多数强奸案件中证明给药情况存在问题。本研究旨在通过GHB给药的替代标志物来延长检测窗口期。在DBA/2J小鼠模型中使用微阵列技术，以检测在暴露后长达96小时的时间里GHB暴露后外周血中的基因表达变化。本研究聚焦于两个变化最为显著的转录物，即表皮调节素和星形胶质细胞富集磷酸蛋白15（Pea-15）。与对照组相比，在给予GHB（1 g/kg）的小鼠中，这两个基因的核糖核酸表达均有所增加（在96小时时分别上调8.5倍和4.6倍）。为了在蛋白质水平上证实这些结果，开发了一种细胞内流式细胞术检测方法，以检测GHB暴露后这两种潜在生物标志物在外周血中的蛋白质水平变化。这些结果表明，经过进一步开发，表皮调节素和Pea-15可能被证明是间接检测GHB给药的重要替代标志物。
