【摘要】 锌诱导兔肝金属硫蛋白 (Zn7-MT)是一种富含半胱氨酸的低分子量的锌结合蛋白 ,在金属代谢和解毒方面起着十分重要的作用。本项研究是采用外源性的MT在鼠原代肝细胞 (RPHC)中 ,对金属铅毒性方面所起的保护作用进行研究。其方法是将RPHC单层培养 2 4小时 ,然后加入一定浓度的 (Zn7-MT)后 ,并将RPHC在各种浓度铅中 ,实施暴露 2 4小时 ,分别测定细胞乳酸脱氢酶的渗出量和K+的损失来评价它们对细胞的毒性作用。同时 ,研究铅在细胞内、外的铅元素的分布和吸收情况 ,以及在Zn7-MT的存在下 ,探讨Zn7-MT在RPHC中对铅毒性方面所起的作用。实验结果证明 ,在Zn7-MT的存在下 ,铅对细胞的毒性作用显著性降低 ,其细胞对铅元素的吸收和聚集产生一定的改变。在对照组细胞的胞质中 ,铅可能主要与高分子量的蛋白结合 ,而在Zn7-MT存在下 ,这些金属可能主要与Zn7-MT相结合更多还原

【Abstract】 Metallothionein (MT), a low-molecular-weight, cysteine-rich, zinc-binding protein, has an important effect in the detoxification of various metals. However, extra Zn 7-MT protects aginst the cellular toxicity of lead in rat primary hepatocyte (RPHC) culture has seldom been examined thoroughly. This study was therefore designed to determine the effects of extra Zn 7-MT on the toxicity of lead in rat primary hepatocyte culture. Hepatocytes were grown in monolayer culture for 24 h and Zn 7-MT was subsequently added for 24 h. RPHC were exporsed to different concentration of lead for 24 h. Cytotoxity was assessed by enzyme leakage and loss of intracellular K +. Meanwhile, the subcellular distribution and accumulation of lead was studied, and the protactive effect on the cellular toxicity of lead in RPHC culture in the present of Zn 7-MT was investigated. The results showed that the toxicity of lead was significantly less in the presence of Zn 7-MT. The hepatocelluar uptake and accumulation of lead have markedly altered. In the cytosol of control cells, the lead was bound mainly to high-molecular-weight proteins whereas the lead was mainly associated with MT in the presence of extra Zn 7-MT.更多还原