Development of an Experimental System by Using Perfused Organs to Study the Combined Effects of Environmental Factors

1.当我们在实际环境中评估化学制剂对我们健康的影响时，我们必须考虑它们的影响的相互干扰。除了考虑化学药剂之间的相互作用外，还考虑了化学药剂与胁迫、营养等环境因素的相互作用。为此，我们开发了一套由扫描反射光谱和器官水平的表面荧光光谱组成的系统。该实验系统使我们能够实时观察大鼠肝脏和肾脏等器官的细胞内生化变化。2.研究了不同基质对大鼠肾脏灌流后能量生产的影响。L乳酸和α-酮戊二酸是维持大鼠肾脏能量代谢的有效底物。3.在应激对三氯乙烯代谢影响的研究中，发现10 nm肾上腺素可提高大鼠肝脏三氯乙烯代谢率。4.在大鼠肝脏灌流模型上观察乙醇对苯乙烯代谢的影响。乙醇可降低大鼠肝脏对苯乙烯的摄取速率。这一比例可能是由于营养状况的变化而改变的。本文研究了抗炎药氟苯那酸(FA)与乙醇在灌流大鼠肝脏中的相互作用。FA在0.1 mM(2 MM)乙醇浓度下对实际情况下可能发生的乙醇氧化有抑制作用。还观察到FA对乙醇氧化的影响随营养条件的变化而变化。在大鼠肾脏灌流模型上，研究了FA对肾脏细胞内能量代谢的解偶联作用。FA降低了降低的Pn水平，降低了Na的部分重吸收和Ca的部分重吸收。提示FA抑制ATP产生的解偶联作用影响了能量依赖性离子转运系统的功能。

1. When we assess the effect of chemical agents on our health in actual environment, we must consider interractions of their effects. In addition to the interactions between chemical agents, the interactions of chemical agents with some environmental factors including stress and nutrition are also taken into the consideration. We have developed a system consisting of scanning reflectance spectrophotometry and surface fluorometry at the organ level for this purpose. This experimental system enables us to observe the real-time intracellular biochemical changes in perfused rat organs like liver and kidney. 2. Contribution of substrates on eneygy production in perfused rat kidney was studied. L-lactate and alpha-ketoglutarate were efficient substrates for rat kidney to maintain energy metabolism. 3. In the study of effect of stress on trichloroethylene metabolism, it was obtained that 10nM epinephrine increased trichloroethlene metabolism rate in rat liver. 4. Effect of ethanol on styrene metabolism was assessed in the perfused rat liver. Ethanol decreased the rate of styrene uptake in rat liver. And it was suggested that the rate was modified due to changes in nutritional condition.5. Interactions of flufenamic acid (FA), an anti-inflammatory drug, and ethanol on their metabolisms were studied in the perfused liver from rats under fed and fasted conditions. FA suppressed ethanol oxidation at the concentrations of 0.1mM (2mM of ethanol) that could occur in the actual situation. It was also observed that the effect of FA on the ethanol oxidation was modified by the nutritional condition. An uncoupling effect of FA on renal intracellular energy metabolism was studied in the perfused rat kidney. FA decreased the reduced PN level, the fractional reabsorption of Na, and the fractional reabsorption of Ca. It was suggested that function of energy dependent ion transport systems was influenced because of uncoupling effect of FA surpressing ATP production.