Armeni T, Ghiselli R, Balercia G, Goffi L, Jassem W, Saba V, Principato G
Institute of Biology and Genetics, Institute of Internal Medicine, Ancona, I-60100, Italy.
J Surg Res. 2000 Feb;88(2):207-14. doi: 10.1006/jsre.1999.5781.
Liver ischemia/reperfusion is frequently associated with organ injury to which reactive oxygen species contribute. The aim of our study was to evaluate cytosolic and mitochondrial glutathione levels and morphological changes in hepatocytes of rat liver in an experimental model of ischemia/reperfusion.
The experimental procedure consisted of temporary interruption of blood flow to the left lateral and medial hepatic lobes for different lengths of time and, in some cases, subsequent reperfusion. Cytosolic and mitochondrial glutathione levels were evaluated and ultrastructural analysis was carried out for all samples.
Ischemic lobes showed ultrastructural changes in relationship with the increase in ischemia time. Total glutathione levels did not show variations in ischemic lobes and sham lobes with respect to control rats during ischemia only. Instead, during reperfusion, significant ultrastructural alterations of the hepatocytes and a significant depletion of glutatione in cytosolic and mitochondrial compartments were evident. The sham lobes also showed a significant glutathione decrement. Increased oxidized glutathione (GSSG) levels were found during ischemia both in ischemic lobes and in sham lobes. During reperfusion GSSG was found to a minor extent, in the cytosolic compartment. In mitochondria GSSG levels were also high during reperfusion.
We conclude that depletion of glutathione contributes to impaired liver after reperfusion following ischemia but depletion of glutathione alone does not induce changes in the morphology of the hepatocytes. Glutathione depletion and a greater quantity of GSSG, even in sham lobes, may indicate a metabolic alteration which spreads to compartments that are not involved in ischemia/reperfusion.
肝脏缺血/再灌注常伴有器官损伤，活性氧在其中起作用。我们研究的目的是在缺血/再灌注实验模型中评估大鼠肝脏肝细胞的胞质和线粒体谷胱甘肽水平以及形态变化。
实验过程包括暂时中断左外侧和内侧肝叶的血流不同时长，部分情况下随后进行再灌注。对所有样本评估胞质和线粒体谷胱甘肽水平并进行超微结构分析。
缺血肝叶显示出与缺血时间增加相关的超微结构变化。仅在缺血期间，缺血肝叶和假手术肝叶的总谷胱甘肽水平相对于对照大鼠未显示出差异。相反，在再灌注期间，肝细胞明显的超微结构改变以及胞质和线粒体区室中谷胱甘肽的显著消耗是明显的。假手术肝叶也显示出显著的谷胱甘肽减少。在缺血期间，缺血肝叶和假手术肝叶中均发现氧化型谷胱甘肽（GSSG）水平升高。在再灌注期间，在胞质区室中发现少量的GSSG。在线粒体中，再灌注期间GSSG水平也很高。
我们得出结论，谷胱甘肽的消耗导致缺血后再灌注时肝脏受损，但仅谷胱甘肽的消耗不会诱导肝细胞形态改变。即使在假手术肝叶中，谷胱甘肽的消耗和更多量的GSSG可能表明一种代谢改变，这种改变扩散到未参与缺血/再灌注的区室。
