Oskarsson A, Fowler B A
Exp Mol Pathol. 1985 Dec;43(3):409-17. doi: 10.1016/0014-4800(85)90077-2.
Exposure of rats to lead in drinking water at concentrations of 500 ppm and 1000 ppm for 3 and 6 months resulted in elevated blood lead levels, formation of kidney intranuclear inclusion bodies, and increased urinary excretion of uroporphyrin and coproporphyrin. The erythrocytic Zn-protoporphyrin was increased in the highest dose group. No significant effects on body weight gain or kidney weight were observed. Renal activity of delta-aminolevulinic acid synthetase (ALAS) was not significantly affected by lead treatment. The renal activity of delta-aminolevulinic acid dehydrase (ALAD) was moderately increased and ferrochelatase activity was significantly decreased. The relatively small effects of chronic lead exposure on renal heme biosynthesis suggests that intracellular complexation of lead with high-affinity renal lead binding proteins (PbBP) and formation of intranuclear inclusions in proximal tubule cells protects this highly sensitive pathway in kidney from lead inhibition in vivo. These data also suggest that the observed increases in urinary porphyrin excretion are primarily due to lead effects on the erythropoietic system.
将大鼠暴露于浓度为500 ppm和1000 ppm的饮用水铅环境中3个月和6个月，导致血铅水平升高、肾细胞核内包涵体形成，以及尿卟啉和粪卟啉的尿排泄增加。最高剂量组的红细胞锌原卟啉增加。未观察到对体重增加或肾脏重量有显著影响。铅处理对δ-氨基乙酰丙酸合成酶（ALAS）的肾脏活性没有显著影响。δ-氨基乙酰丙酸脱水酶（ALAD）的肾脏活性适度增加，而亚铁螯合酶活性显著降低。慢性铅暴露对肾脏血红素生物合成的影响相对较小，这表明铅与高亲和力的肾脏铅结合蛋白（PbBP）在细胞内络合，以及近端小管细胞核内包涵体的形成，在体内保护了肾脏中这条高度敏感的途径免受铅的抑制。这些数据还表明，观察到的尿卟啉排泄增加主要是由于铅对红细胞生成系统的影响。
