Bergasa N V, Vergalla J, Swain M G, Jones E A
Liver Diseases Section, National Institutes of Health, Bethesda, Maryland, USA.
Liver. 1996 Oct;16(5):298-302. doi: 10.1111/j.1600-0676.1996.tb00749.x.
The liver of adult rats with cholestasis secondary to bile duct resection has been shown to express the proenkephalin gene and, by immunohistochemical stains, to contain met-enkephalin. To further study hepatic opioids in cholestasis, concentrations of proenkephalin-derived endogenous opioids were measured in a rat model of cholestasis by the use of radioimmunoassays. The specificity of the immunoreactivity detected by the assays was confirmed by high performance liquid chromatography (HPLC). In adult male rats with cholestasis due to BDR, the concentrations of three proenkephalin-derived opioid peptides were increased. Specifically, the mean hepatic concentrations of met-enkephalin, Met-Enk-Arg6-Phe7 and leu-enkephalin were 2.5 (p < 0.005), 2.1 (p < 0.005) and 2.5 (p < 0.01) fold higher than the corresponding mean for controls. These findings provide further independent evidence that opioid peptides accumulate in the liver in a model of cholestasis and are consistent with de novo synthesis of opioid peptides occurring in the cholestatic liver. This phenomenon may have relevance to the altered function of the opioid system in cholestasis and to the role of the liver as a neuroendocrine organ.
已证明，在因胆管切除继发胆汁淤积的成年大鼠肝脏中，前脑啡肽基因会表达，且通过免疫组织化学染色发现肝脏中含有甲硫氨酸脑啡肽。为进一步研究胆汁淤积时肝脏中的阿片样物质，利用放射免疫分析法在胆汁淤积大鼠模型中测定了前脑啡肽衍生的内源性阿片样物质的浓度。通过高效液相色谱法（HPLC）证实了该分析法检测到的免疫反应性的特异性。在因胆管切除导致胆汁淤积的成年雄性大鼠中，三种前脑啡肽衍生的阿片肽浓度升高。具体而言，甲硫氨酸脑啡肽、甲硫氨酸脑啡肽 - 精氨酸6 - 苯丙氨酸7和亮氨酸脑啡肽的平均肝脏浓度分别比对照组相应平均值高2.5倍（p < 0.005）、2.1倍（p < 0.005）和2.5倍（p < 0.01）。这些发现提供了进一步的独立证据，表明在胆汁淤积模型中阿片肽在肝脏中蓄积，并且与胆汁淤积肝脏中发生的阿片肽从头合成一致。这种现象可能与胆汁淤积时阿片样物质系统功能改变以及肝脏作为神经内分泌器官的作用有关。
