Effects of Hypoxia and Environmental Agents on Renal Tubules with a Scope of Combined Effect

当我们在实验动物中评估多种因子的联合作用并将其推广到人类时，这些因子在活体器官中相互作用的数据推导机制显然是有帮助的。因此，我们开发了体内扫描反射分光光度法和体内表面荧光法，用于实时观察细胞内生化变化，以便将该技术应用于兔肾近端小管和灌注大鼠肾的环境和职业毒理学研究。乳酸脱氢酶（乳酸脱氢酶）释放量作为质膜损伤的指标。测定了细胞中钾、钙的含量。Ca含量在缺氧时略有下降，但在严重缺氧时增加了四倍。缺氧和缺氧时呼吸损伤程度相同，提示Ca积累与呼吸损伤无关。将胞外钙浓度降低至2.5 < micmicr>可显著降低缺氧时LDH的释放，提示缺氧时质膜损伤可能与细胞内游离钙的增加有关。有机溶剂对细胞损伤的影响在管状细胞悬液中进行了评估，并在综合作用范围内进行了评估。本研究中使用的有机溶剂在低浓度时增加了管状细胞的耗氧量，而在相对高浓度时则减少了耗氧量。本研究将小球细胞悬浮液和灌注肾作为评价多种环境因子联合作用的实验模型。

When we assess the combined effect of plural agents in the experimental animals for extrapolation to human, the data eliciting mechanisms about their interactions in the living organ are obviously helpful. Thus, we have developed in vivo scanning reflectance spectrophotometry and in vivo surface fluorometry for this purpose of the real-time observation of intracellular biochemical changes in order to apply the techniques to the studies in environmental and occupational toxicology in rabbit proximal renal tubules and in perfused rat kidney. The release of lactate dehydrogenase (LDH) was measured as an index of plasma membrane damage. The cellular contents of K and Ca were also measured. Ca content decreased slightly during anoxia, but increased up to fourfold during severe hypoxia. The degree of respiratory impairment was identical during anoxia or hypoxia, suggesting that Ca accumulation was not associated with the impairment. Decreasing the extracellutar Ca to 2.5 <micrn> decreased LDH release significantly during anoxia, suggesting that plasma membrane damage during anoxia may be associated with increased intracellular free Ca. Effects of organic solvents on cell injury were assessed in the tubular cell supsension with a scope of combined effect. The organic solvents employed in this study increased oxygen consumption in the tubular cells at its low concentrations, whereas they decreased the oxygen consuption at relatively high concentrations. Both bubular cell suspension and perfused kindney in the present study were considered as an experimental model for assessment of combined effects of plural environmental agents.