甲基苯丙胺（MA）滥用和HIV感染是当今全球最严重两大公共卫生问题，MA与HIV-Tat蛋白对神经元损害有着显著的协同作用，均能导致神经元变性、坏死和凋亡。Nrf2-ARE是一种新型抗氧化信号通路，具有抗氧化应激、调节炎症损伤、拮抗细胞凋亡等作用。我们前期研究发现MA与HIV-Tat蛋白能协同诱导多巴胺能神经元自噬，氧化应激可能是其自噬的基础，但协同机制尚不明确。本研究采用综合方法包括电镜、免疫双标、共聚焦荧光显微镜、流式细胞仪、高效液相、RT-PCR及蛋白印迹等技术，从体内和体外水平检测氧化应激因子、自噬及相关自噬信号通路改变，明确氧化应激的作用，并观察Nrf2-ARE信号通路及调控的下游靶基因影响，以阐明Nrf2在MA与HIV-Tat蛋白协同诱导多巴胺神经元自噬的保护作用及其信号调控机制，为毒品滥用的HIV感染者（特别是艾滋病痴呆）提供新的干预靶标。

Methamphetamine (MA) abuse and human immunodeficiency virus (HIV) infection are the most serious public health problems all over the world. Recent studies have indicated that MA and HIV-Tat protein have obvious synergistic effects on neuronal damage. HIV-Tat protein and methamphetamine abuse can lead to degeneration, necrosis and apoptosis of neurons. Nuclear factor-E2 - related factor (Nrf2) plays a critical role in the regulation of cellular redox status. The Nrf2-ARE pathway is considered as the new antioxidant pathway, and the antioxidant’s effects involve in antioxidative stress, regulating inflammatory injury, anti-apoptosis and so on. Our previous studies found that methamphetamine and HIV-1 Tat protein could induce synergistically dopaminergic neuron's autophagy, and the oxidative stress might be the basis of autophagy, but the synergistic mechanisms are not clear yet. In vivo and in vitro, the present study aims to detect the level of oxidative stress, autophagy and autophagic signaling pathway changes, as well as to observe the downstream target genes of Nrf2-ARE signaling pathway and regulation effect by electron microscope, double immunohistochemical staining, confocal fluorescence microscopy, flow cytometry, HPLC, RT-PCR and Western blotting. The aim is to clear out the role of oxidative stress, the signal rugulation mechanism and protective effect of Nrf2 pathway in dopaminergic neuron's autophagy induced synergistically by methamphetamine and HIV-1 Tat protein. We are looking forward to find a new target in the methamphetamine abuse and HIV (AIDS Dementia Complex, ADC).