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

利用灌注器官开发实验系统来研究环境因素的综合影响

基本信息

批准号：
01480204
负责人：
TAKANO Takehito
金额：
$ 4.74万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

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.

1.在评价实际环境中化学制剂对人体健康的影响时，必须考虑其影响的相互影响。除了化学制剂之间的相互作用，化学制剂与一些环境因素，包括压力和营养的相互作用也被考虑在内。为此，我们开发了一个系统，包括扫描反射分光光度法和表面荧光法在器官水平。该实验系统使我们能够实时观察灌流大鼠肝脏和肾脏等器官的细胞内生化变化。2.本文研究了不同底物对灌流大鼠肾脏产能的影响。L-乳酸和α-酮戊二酸是大鼠肾脏维持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肾上腺素可增加大鼠肝脏三氯乙烯代谢速率。4.在灌流的大鼠肝脏中评估乙醇对苯乙烯代谢的影响。乙醇降低大鼠肝脏对苯乙烯的摄取率。并建议根据营养状况的变化，对该比例进行调整.在大鼠肝脏灌流中研究了抗炎药氟芬那酸（FA）和乙醇在进食和禁食条件下对它们代谢的相互作用。FA在0.1mM（2 mM乙醇）浓度下抑制乙醇氧化，这可能发生在实际情况中。同时还观察到，营养条件对FA对乙醇氧化的影响有一定的调节作用。在灌流大鼠肾脏中研究了FA对肾脏细胞内能量代谢的解偶联作用。FA降低了PN水平、Na重吸收分数和Ca重吸收分数。提示FA抑制ATP产生的解偶联效应影响了能量依赖性离子转运系统的功能。