镉致Redox平衡失调氧化损伤的时效、量效与干预机制的研究

我国很多地区土壤中镉污染严重，镉中毒可以导致以骨和肾为主的多脏器损伤。然而，镉中毒的机制还不明确，镉中毒的防治形势还很严峻。文献和我们的研究进展表明，镉中毒存在明显的氧化应激损伤，然而具体分子机制还有待研究。本项目拟采用不同剂量镉构建细胞和大鼠镉中毒模型，观察不同时间的毒效应以及相关干扰因素和抗氧化干预对镉毒性的影响，探索镉毒性致氧化应激损伤特点，证明镉污染引起氧化应激是导致脏器损伤的决定因素，镉引起脏器Redox平衡失调的程度决定脏器损伤的差异等机制。通过明确"镉--Redox平衡失调--中毒"的分子机制，有望阐明上述发病机制假说中有待证明的关键环节，对系统认识镉中毒的发病机制及采取有针对性的防治策略有重要的理论和实践意义，为人群防治镉污染的危害提供新的思路。

Contamination of Cadmium in soil of many parts of China is severe. Cadmium poisoning causes the injury of bone, kidney and many other organs. However, the mechanism of Cadmium poisoning is still not clear. Prevention and control of the situation of Cadmium poisoning is rigorous. Based on literature and our previous results, it is shown that Cadmium poisoning causes evident oxidative stress. However, the mechanism of Cadmium-induced oxidative stress is still to be elucidated. In the present project, we aimed to establish cell and animal model of Cadmium poisoning using different doses of Cadmium; observe Cadmium-induced toxicity time-dependently; observe the effect of antioxidant treatment on Cadmium-induced toxicity; explore the characteristic of Cadmium-induced oxidative stress; verify that oxidative stress is the determinant factor of Cadmium-induced injury; verify that the degree of injury is dependent upon the degree of disorder of redox balance induced by Cadmium. Through elucidating the molecular mechanism of "Cadmium-disorder of redox balance-poisoning", we try to elucidate the key step in the hypothesis, provide theoretical and practical evidence for the insight into the pathogenesis and preventive strategy of Cadmium poisoning.