Memorial University of Newfoundland, Department of Biochemistry, St. John's, NL A1B 3X9, Canada.
Can J Physiol Pharmacol. 2013 May;91(5):362-8. doi: 10.1139/cjpp-2012-0060. Epub 2012 Dec 19.
There is functional zonation of metabolism across the liver acinus, with glutamine synthetase restricted to a narrow band of cells around the terminal hepatic venules. Portacaval anastomosis, where there is a major rerouting of portal blood flow from the portal vein directly to the vena cava bypassing the liver, has been reported to result in a marked decrease in the activity of glutamine synthetase. It is not known whether this represents a loss of perivenous hepatocytes or whether there is a specific loss of glutamine synthetase. To answer this question, we have determined the activity of glutamine synthetase and another enzyme from the perivenous compartment, ornithine aminotransferase, as well as the immunochemical localization of both glutamine synthetase and ornithine aminotransferase in rats with a portacaval shunt. The portacaval shunt caused a marked decrease in glutamine synthetase activity and an increase in ornithine aminotransferase activity. Immunohistochemical analysis showed that the glutamine synthetase and ornithine aminotransferase proteins maintained their location in the perivenous cells. These results indicate that there is no generalized loss of perivenous hepatocytes, but rather, there is a significant alteration in the expression of these proteins and hence metabolism in this cell population.
肝脏腺泡存在代谢的功能分区,谷氨酰胺合成酶局限于终末肝小静脉周围的细胞窄带。门腔静脉吻合术(将门静脉的血流主要从门静脉直接绕过肝脏重新引流入腔静脉)可导致谷氨酰胺合成酶的活性显著降低。目前尚不清楚这是否代表了窦周细胞的丧失,还是存在谷氨酰胺合成酶的特异性丧失。为了解决这个问题,我们已经在患有门腔静脉分流的大鼠中确定了谷氨酰胺合成酶和来自窦周隔室的另一种酶,鸟氨酸氨基转移酶的活性,以及谷氨酰胺合成酶和鸟氨酸氨基转移酶的免疫化学定位。门腔静脉分流导致谷氨酰胺合成酶活性显著降低,鸟氨酸氨基转移酶活性增加。免疫组织化学分析表明,谷氨酰胺合成酶和鸟氨酸氨基转移酶蛋白保持在窦周细胞中的位置。这些结果表明,不存在窦周肝细胞的普遍丧失,而是这些蛋白的表达以及因此该细胞群体中的代谢发生了显著改变。