Plasma cadmium-metallothionein, new and ideal biomarker, based on its mechanism

人们认为，当肾皮质镉含量超过200 μg/g时，镉会诱发肾功能障碍（WHO, 1992）。由于镉在肾皮质的生物半衰期很长，如20-30年，镉诱发的肾功能障碍被认为不会恢复（WHO, 1992）。然而，镉引起的肾功能障碍在镉暴露终止后确实是可逆的。我们提出了镉诱发肾功能障碍的机制：(1)镉进入人体后，以镉金属硫蛋白（CdMT）的化学形式在肝脏中积累；(2)镉诱发肝功能障碍；(3)镉金属硫蛋白从肝脏渗漏到血液中；(4)镉金属硫蛋白分子较小，容易通过肾小球（6000）；(5)镉金属硫蛋白在肾小管处被重吸收。(6) CdMT分裂为镉离子和金属硫蛋白；(7)镉离子损伤肾小管膜导致肾功能障碍（Nomiyama and Nomiyama, 1994）。以下结果证实了我们提出的镉诱导功能障碍的机制：(1)暴露水平不同，肾皮质镉的临界浓度不同，日剂量为0.3、1和3 μgCd/ kg时，肾皮质镉的临界浓度分别为275、296和222 μgCd/g。相反，(2)日剂量为0.3、1和3 mgCd/kg的家兔血浆镉金属硫蛋白（CdMT）临界浓度均为60 ~ 75μ gcd /l。(3)终止镉暴露后，镉所致肾功能障碍随着血浆CdMT的降低而逆转。(4)肝功能调节剂甘草酸对镉所致肾功能损害有预防作用。

Cadmium has been believed to induce renal dysfunction when cadmium in the renal cortex exceeds 200 μg/g (WHO, 1992). Because the biological half time cadmium in the renal cortex is very long such as 20-30 years, cadmium-induced renal dysfunction has been believed not to recover (WHO, 1992). However, it is true that cadmium-induced renal dysfunction is reversible after termination of cadmium exposure. We then proposed the mechanism of cadmium-induced renal dysfunction as follows : (1) cadmium taken into the body accumulates in the liver in a chemical form of cadmium-metallothionein (CdMT), (2) cadmium induces hepatic dysfunction, (3) CdMT leaked out from the liver into the blood stream, (4) CdMT easily passes through glomeruli because of its smaller molecular size (6,000), (5) and then it is reabsorbed at the renal tubules. (6) CdMT was split into cadmium ion and metallothionein, (7) cadmium ion injures tubular membrane to result in renal dysfunction (Nomiyama and Nomiyama, 1994).The following results approved our proposed mechanism of cadmium-induced dysfunction : (1) critical concentration of cadmium in the renal cortex varied with exposure level, such as 275, 296 and 222 μgCd/g in rabbits given cadmium at a daily dose of 0.3, 1 and 3 mgCd/kg. On the contrary, (2) the critical concentration of plasma cadmium metallothionein (CdMT) in rabbits given cadmium at a daily dose of 0.3, 1 and 3 mgCd/kg was the same as 60-75μgCd/l. (3) After termination of cadmium exposure, cadmium-induced renal dysfunction was reversed with the decrease in plasma CdMT. In addition, (4) glycyrrhizin, hepatic function modifier, prevented cadmium-induced renal dysfunction.