Anundi I, Kauffman F C, te Koppele J M, Yamanaka H, Whittaker M, Popp J A, Thurman R G
Department of Pharmacology, University of North Carolina, Chapel Hill 27514.
Cancer Res. 1989 Jun 15;49(12):3282-6.
Fluorescein-isothiocyanate dextran (FITC-dextran), a dye confined to the vascular space, was infused via the hepatic artery and portal vein into perfused livers from fed rats treated with diethylnitrosamine for 4 to 5 months. Fluorescence due to FITC-dextran was detected with fiberoptic microlight guides placed on surface nodules of about 5 mm in diameter. Nodules were categorized into groups with normal and compromised microcirculation based on their fluorescence following infusion of FITC-dextran. Similar results were obtained when nodules were classified based on reflectance of trypan blue. Despite compromised microcirculation, ATP and ADP levels as well as ATP/ADP ratios were comparable in both groups of nodules; however, AMP was elevated in FITC-dextran-negative nodules (i.e., those with compromised microcirculation). Nodules with compromised microcirculation also contained higher glucose and lactate levels than nodules that were well perfused; however, glycogen was five times lower than in FITC-dextran-positive nodules. Fasting reduced ATP/ADP ratios in poorly perfused nodules in comparison to well-perfused nodules. In perfused livers from fed rats where glycogen was high, however, ATP/ADP ratios and rates of ATP depletion during ischemia were the same in well-perfused and poorly perfused nodules. Products of glycogen breakdown (e.g., glucose and lactate) were elevated in nodules from livers of fed but not fasted rats. The results indicate that alteration of perfusion of hepatic nodules does not change ATP levels nor the capacity of nodules to utilize high energy phosphate during anoxia. Thus, near normal energy status is maintained from glycogen metabolism in poorly perfused nodules via glycolysis. Since basal ATP content and utilization is comparable in well and poorly perfused nodules, compromised energy status is unlikely to explain selection of nodules that regress to near normal hepatocytes.
异硫氰酸荧光素葡聚糖（FITC-葡聚糖）是一种局限于血管空间的染料，通过肝动脉和门静脉注入用二乙基亚硝胺处理4至5个月的喂食大鼠的灌注肝脏中。通过放置在直径约5毫米的表面结节上的光纤微光导检测FITC-葡聚糖产生的荧光。根据注入FITC-葡聚糖后结节的荧光，将结节分为微循环正常和受损的组。当根据台盼蓝的反射率对结节进行分类时，也获得了类似的结果。尽管微循环受损，但两组结节中的ATP和ADP水平以及ATP/ADP比值相当；然而，FITC-葡聚糖阴性结节（即微循环受损的结节）中的AMP升高。微循环受损的结节中的葡萄糖和乳酸水平也高于灌注良好的结节；然而，糖原比FITC-葡聚糖阳性结节中的低五倍。与灌注良好的结节相比，禁食降低了灌注不良结节中的ATP/ADP比值。然而，在糖原含量高的喂食大鼠的灌注肝脏中，灌注良好和灌注不良的结节中ATP/ADP比值以及缺血期间ATP消耗率是相同的。喂食但未禁食的大鼠肝脏结节中糖原分解产物（如葡萄糖和乳酸）升高。结果表明，肝结节灌注的改变不会改变ATP水平，也不会改变结节在缺氧期间利用高能磷酸盐的能力。因此，灌注不良的结节通过糖酵解从糖原代谢中维持接近正常的能量状态。由于灌注良好和灌注不良的结节中基础ATP含量和利用率相当，能量状态受损不太可能解释回归到接近正常肝细胞的结节的选择。
