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

缺氧和环境因素对肾小管的影响及其联合作用范围

基本信息

批准号：
61480163
负责人：
TAKANO Takehito
金额：
$ 2.56万
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：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

项目摘要

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.

当我们在实验动物中评估多种药物的综合效应并外推到人类时，得出有关它们在活器官中相互作用的机制的数据显然是有帮助的。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来实时观察细胞内的生化变化，以便将该技术应用于兔近端肾小管和灌注大鼠肾脏的环境和职业毒理学研究。测量乳酸脱氢酶（LDH）的释放作为质膜损伤的指标。还测量了 K 和 Ca 的细胞含量。缺氧时钙含量略有下降，但严重缺氧时钙含量增加至四倍。缺氧或缺氧期间呼吸损伤的程度是相同的，这表明Ca积累与损伤无关。将细胞外 Ca 减少至 2.5 µ微米，缺氧期间 LDH 释放显着减少，表明缺氧期间质膜损伤可能与细胞内游离 Ca 增加有关。在肾小管细胞悬浮液中评估有机溶剂对细胞损伤的影响，并具有一定范围的综合作用。本研究中使用的有机溶剂在低浓度下增加了管状细胞的耗氧量，而在相对高浓度下则降低了耗氧量。本研究中的管状细胞悬液和灌注肾都被认为是评估多种环境因素联合效应的实验模型。