外向钾电流在gp120, 甲基苯丙胺引起海马神经元损伤致HIV相关性痴呆中作用及机制

项目名称： 外向钾电流在gp120, 甲基苯丙胺引起海马神经元损伤致HIV相关性痴呆中作用及机制

项目编号： No.81202230

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 王军

作者单位： 南京医科大学

项目金额： 23万元

中文摘要： 电压依赖性钾通道（Kv）是广泛分布的、种类繁多的一大类离子通道，最近研究表明，钾离子通道和细胞凋亡密切相关。本项目以外向型钾离子通道(Kv2.1,Kv4.2)作为研究靶点，探讨HIV壳蛋白gp120在形成HIV相关性痴呆过程中的作用，同时结合艾滋病重要的行为学因素-毒品吸食，并以甲基苯丙胺（Methamphetamin，Meth）为代表，利用全细胞膜片钳技术结合Real-time PCR，Western-Blot，TUNEL，细胞转染等技术从电流增大现象到相关亚型钾通道及其相关调节蛋白的表达，阐述相关信号通路变化，以期为HIV相关性痴呆（HAD）的防治提供可能的治疗靶点及理论支持。同时，该研究致力于gp120和Meth协同作用的探讨，将有助于阐述Meth在HAD形成过程中的作用，具有重要现实意义。

中文关键词： 甲基苯丙胺；gp120；HIV相关性痴呆；钾通道；神经元损伤

英文摘要： The voltage-dependent K+ channels are wide broad of channels that with varied isotypes. Recent data show that the K+ channels are closely associated with the cell apoptosis. In the present work, we will explore the effects of gp120 on the outward K+ currents and clarify the relationship between the K+ currents and the neural damage which is a hallmarker for HIV associated dementia(HAD).In addition, the risk behavior factor of AIDS-"drug abusing"is also mentioned. Methaphetamine(Meth), one of the most "popular"drug in the world， is studied for its influence on the outward K+ currents. Moreover, the isotype of the K+ channel(Kv2.1 and Kv4.2), regulatory proteins and mechanisms are detailed elucidated with the assays of Realtime-PCR,Western-Blot,TUNEL,cell transfection et al. Identification of Kv channels as the targets for gp120 and Meth induced neural damage may open new avenues for therapeutic modalities for HAD. Meantime, the work for synthetic effects of gp120 and Meth on HAD formation will make a full elucidation of the process and show significance for AIDS prevention.

英文关键词： methamphetamine；gp120；HIV associated dementia；K+ channel；neural damage