Bergasa N V, Sabol S L, Young W S, Kleiner D E, Jones E A
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Am J Physiol. 1995 Feb;268(2 Pt 1):G346-54. doi: 10.1152/ajpgi.1995.268.2.G346.
Cholestatic liver disease is associated with clinical and experimental findings consistent with increased opioidergic neuromodulation, increased plasma total opioid activity, and elevated plasma enkephalin concentrations. In contrast to the normal adult rat liver, preproenkephalin mRNA was detected by Northern blotting in livers of adult rats with cholestasis due to bile duct resection and not in the sham-resected controls. Preprodynorphin mRNA was not detected in livers of either group, while preproopiomelanocortin mRNA was found in very low levels in both groups. Preproenkephalin mRNA was not expressed in the livers of rats with acute hepatocellular necrosis induced by thioacetamide. Hybridization histochemistry of cholestatic livers demonstrated the presence of preproenkephalin mRNA primarily over cells in the periportal areas, some of which appeared to be proliferating bile ductular cells. Immunohistochemical staining of cholestatic liver indicated the production of at least Met-enkephalin in association with preproenkephalin gene expression. These findings suggest that the liver itself, by synthesizing enkephalins, contributes directly to the abnormalities of the opioid system reported in cholestasis.
胆汁淤积性肝病与一些临床和实验结果相关，这些结果与阿片样物质神经调节增加、血浆总阿片样物质活性升高以及血浆脑啡肽浓度升高一致。与正常成年大鼠肝脏不同，通过Northern印迹法在因胆管切除导致胆汁淤积的成年大鼠肝脏中检测到前脑啡肽原mRNA，而在假手术切除的对照组中未检测到。两组大鼠肝脏中均未检测到前强啡肽原mRNA，而两组中前阿黑皮素原mRNA水平都非常低。硫代乙酰胺诱导的急性肝细胞坏死大鼠肝脏中未表达前脑啡肽原mRNA。胆汁淤积性肝脏的杂交组织化学显示，前脑啡肽原mRNA主要存在于汇管区周围的细胞中，其中一些细胞似乎是增殖的胆小管细胞。胆汁淤积性肝脏的免疫组织化学染色表明，至少甲硫氨酸脑啡肽的产生与前脑啡肽原基因表达有关。这些发现表明，肝脏自身通过合成脑啡肽，直接导致了胆汁淤积中报道的阿片样物质系统异常。
