镉毒性分子机制及评价方法的研究进展

Research progress on molecular mechanisms and evaluation methods of cadmium toxicity

镉是一种环境重金属,可引起多种毒性反应,也是药物毒理学研究中的重要阳性药物。镉毒性效应相互关联使其分子机制变得十分复杂。本文综述了镉毒性最重要的几种分子机制,包括基因表达改变、抑制受损DNA修复、干扰细胞凋亡及细胞自噬和诱导氧化应激反应。并根据镉毒性分子机制和主要毒靶器官,总结了相应的评价指标及临床前安全性评价方法,如组织病理学检查、镉含量检测、氧化还原状态检测(酶抗氧化系统与非酶抗氧化系统的标志物测定)、免疫印迹法和酶联免疫吸附法检测相关蛋白与酶含量、实时酶聚合链式反应评价相应的基因表达状况等。进而为镉毒性的分子机制探究及镉类似机制的药物安全性评价提供建议。

Cadmium is an environmental heavy metal that can cause a variety of toxic reactions and is also an important positive control drug in drug toxicology research.The interrelated toxic effects of cadmium make its molecular mechanisms very complicated.The most important molecular mechanisms of cadmium toxicity were summarized in this article,including changes in gene expression,inhibition of damaged DNA repair,interference with cell apoptosis and autophagy,and induction of oxidative stress.Based on the molecular mechanisms and main target organs of cadmium toxicity,corresponding evaluation indicators and safety evaluation methods were summarized,such as histopathological examination,cadmium content detection,redox status detection(enzyme antioxidant system and non-enzyme antioxidant system marker determination),Western blotting and enzyme-linked immunosorbent assay for protein and enzyme content detection,and real-time polymerase chain reaction for gene expression detection.The article aimed to provide information for the exploration of potential molecular mechanisms of cadmium toxicity and for the safety evaluation of drugs with cadmium-like mechanisms.