中文摘要
朱砂为含汞矿物药,《中国药典》收载含朱砂的儿科专用制剂14种,儿童对于低剂量的汞暴露较成年人有更高的易感性。我们前期研究发现:幼年小鼠服用朱砂,汞更易蓄积在脑组织中;朱砂可能影响幼虫期秀丽线虫的神经发育。含朱砂儿科制剂的安全性研究尤为重要。本项目拟研究小儿中成药“一捻金”中朱砂的潜在神经发育毒性及配伍减毒:用幼年大鼠研究“一捻金”全方对朱砂中汞吸收、蓄积的影响及其汞形态变化,结合毒代动力学和毒性效应(TK-TD)研究,明确“一捻金”中朱砂潜在神经发育毒性的剂量-时间-毒性关系,确认“一捻金”全方对朱砂神经发育毒性的减毒作用。应用秀丽线虫模型,拆方研究“一捻金”对朱砂神经发育毒性的减毒效应;用对汞毒性敏感性更高的多药耐药蛋白(MRP-7)基因敲低线虫,阐明基于MRP-7介导的“一捻金”对朱砂神经发育毒性的配伍减毒机制,为其用药安全提供科学依据,并为含汞矿物药的安全性评价提供新方法。
英文摘要
Cinnabar, mineral containing mercury, has been used in traditional Chinese medicine (TCM) with long history. "China Pharmacopoeia" records herbal preparations containing cinnabar, in which 14 kinds of them are specific for infants and children. Children are more susceptible than adults to the exposure of low-dose mercury. Our previous study found that young mice accumulated more mercury in brain tissue than adults after taking cinnabar; cinnabar may affect the neural development of C. elegans at larval stage. There have increasing concerns about the safety of pediatric medicine comprising cinnabar. The present project plan to study the potential developmental neurotoxicity of cinnabar and detoxification of pediatric medicine “Yinian Jin” as follows:.To investigate the effect of "Yinian Jin" in whole formulae on absorption and accumulation of mercury in cinnabar and changes in species of mercury in weanling rats. To determine the dose-time-effect relationships of the developmental neurotoxicity for oral administration of cinnabar by conducting TK-TD study. To investigate whether whole formulae of "Yinian Jin" reduce the developmental neurotoxicity induced by cinnabar. .Application of the model organism C. elegans during larval stage, to further study whether other TCM compatibility in "Yinian Jin" decrease developmental neurotoxicity of cinnabar; using a higher sensitivity to mercury toxicity model, multidrug resistance protein (MRP-7) knockdown nematode C. elegans, investigate the compatibility detoxification mechanism of "Yinian Jin" mediated by MRP-7 , in order to explore its rationality of the prescription. .This study will provide scientific evidences for safe use of "Yinian Jin" in clinic and to provide a new method for safety evaluation of mineral TCM containing mercury.
