发育期铅损伤学习记忆是一个不可逆难治性问题，公认损伤机制为铅干扰NMDA谷氨酸离子型通道影响海马LTP产生。新近发现AMPAR亚基GluR1、GluR2在海马LTP及学习记忆产生与维持中起重要作用，而GRIPs是AMPAR运输、锚定调控蛋白，本项目预实验表明铅中毒后能导致GluR2在齿状回、海马门区CA1、CA3区呈斑块状分布；GRIP以及NEEP21均表达升高，尤以GRIP表达增加最为明显。基于此本项目拟在大鼠在体、海马脑片、细胞培养结合形态学、分子生物学、电生理技术研究新生大鼠铅中毒对GluR2调控蛋白、AMPAR亚基表达影响，确立海马LTP损伤与AMPA受体功能变化之间关系，阐明关键蛋白GRIPs表达升高是导致GluR2亚基膜向掺入、内吞循环加速，从而影响LTP时含GluR2 AMPA受体在突触后膜区移除，进而导致LTP损伤的假说，为全面阐明铅损伤学习记忆机制提供新的实验依据。

Developmental exposure to Pb results in irreversible impairment to learning and memory. It has been reported that Pb disturbs the NMDA receptor-mediated LTP. Recent studies indicated that GluR1 and GluR2, two major subunits of the AMPA receptor (AMPAR), play a key role in the LTP generation and learning and memory processes. GRIP is a regulatory protein which involve in the generation, transport and anchor of the AMPAR. Our previous experiments showed that GluR2 expressed in homogeneously in the dentate gyrus, Hilus, CA1 and CA3 of the Hippocampus after Pb exposure, which was accompanied with the markedly increased expression of GRIP and moderate increase of NEEP21. The aim of this study is to investigate the effect of lead on cerebral GluR2, APMAR expression in newborn rats, and to explore the relationship between hippocampal LTP impairment and the functions of APMAR in vivo and in vitro. With advanced molecular biological and electricphysiological technologies, we will prove our hypothesis that the elevated expression of GRIPs results in a translocation of AMPAR to the basement membrane and accelerated endocytosis cycle, further influence the remove of GluR2 AMPA receptor from postsynaptic membrane during LTP. This study will be helpful to clarify the mechanisms of Pb-induced impairment of learning and memory.