重复性注射镉金属硫蛋白致小鼠肾脏损伤的时程变化

Time course of renal impacts induced by multiple short-interval injections of cadmium-metallothionein in mice

目的 探讨重复性短时间间隔皮下注射镉金属硫蛋白 (CdMT)对实验小鼠肾脏损伤的时程变化。方法 染毒组小鼠给予首次高剂量 (0 0 5mg/kg)和随后重复 4次相同低剂量 (0 0 2 5mg/kg)的CdMT ,每次间隔时间为 2h ,在首次染毒后 12、2 4、72、16 8和 336h处死动物 ,对照组注射相同体积的生理盐水。观察肝、肾皮质组织中镉、钙以及尿液中镉、钙及尿蛋白的变化情况。结果 皮下注射CdMT后 ,肾皮质中钙含量均高于对照组 ,在染CdMT后第 2 4及 336h肾皮质钙含量明显升高 ,且随着时间的延长尿蛋白、尿钙也有升高的趋势 ,尿蛋白、尿钙的高峰均出现在注射CdMT后 16 8h。结论 重复性短时间间隔皮下注射CdMT造成小鼠肾脏损害可维持较长的时间 ,钙稳态失衡是可能的毒作用机制之一。

Objective To explore the time course of the renal impacts induced by multiple short interval injections of cadmium metallothionein (CdMT) in female mice.Methods The mice were given with an initial high dose and with four subsequent low doses (0.05+4×0 025 mg/kg) subcutaneously at 2 h intervals. The excretion of cadmium, calcium and protein in urine and changes of calcium and level in kidney cortex were studied following the first injection. Results The calcium level in kidney cortex were significantly higher at 24 and 336 h after the first injection. The excretion of calcium and protein in urine appeared to be markedly increased to a maxiumal value at 168 h and kept until 336 h. Conclusion Marked nephrotoxic effects after multiple short interval CdMT injections were shown with rather long duration. The disturbance of calcium homeostasis might be one of the possible mechanisms of such renal impacts.