MRPs在肾脏镉转运中的作用研究

镉作为重要的环境和职业污染物一直都是公共卫生关注的热点。镉可以蓄积在体内对多个器官产生损伤，其中肾脏是体内镉蓄积的主要靶器官，长期职业性和生活性镉接触主要引起肾脏损伤。减少镉在肾脏组织和细胞中的蓄积，对于预防和治疗镉中毒引起的机体损伤，尤其是肾脏的损伤至关重要。多重耐药相关蛋白MRPs，是ATP能量依赖性跨膜蛋白，能够转运多种外源和内源性物质，近期发现MRPs还能够转运一些重金属。如果MRPs在肾脏镉转运中发挥作用，那么针对MRPs蛋白的调控可能成为治疗和预防镉中毒的靶点。首先，本研究通过体内和体外实验，利用基因调控技术和一些生物化学相关技术探讨MRPs蛋白家族在肾脏组织和细胞镉转运中的作用；其次通过实验结合计算机辅助药物设计技术，筛选合成针对调控MRPs的小分子药物，并通过细胞和动物实验验证其效果。该研究将为针对MRPs的靶向精准医疗奠定基础，并为治疗和预防镉中毒引起的肾脏毒性提供支持。

As an important environmental and occupational pollutants, cadmium poisoning is a hot topic of public health. Cadmium can be accumulated in body, and cause multiple organ damage. kidney is the main target organs. Cadmium exposure main cause kidney damage. Reducing cadmium accumulation in kidney is conducive to prevention and treatment of cadmium poisoning, especially the kidney injury. MRPs is an ATP energy dependent transmembrane protein, and it can transport many kinds of exogenous and endogenous substrates. We discovered MRPs can also transport several heavy metals. If the MRPs can promote the efflux of cadmium in kidney, MRPs regulation may become the target of treatment and prevention of cadmium poisoning. In this study, firstly, in vivo and vitro experiments. Gene regulation technology was first used to study on the effect of MRPs protein family on the transportation of cadmium in kidney ; Secondly, combined the technology of computer aided drug design, we want to synthesize and screen small molecule drugs for regulating the MRPs, and the effect of the drugs will be verified by cells and animal experiments in this study. This study will provide theoretical and technical support for the treatment and prevention of cadmium poisoning caused by renal toxicity.