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目的:评价核因子E2相关因子2 (Nrf2)在μ-δ异源二聚体下调兴奋性氨基酸转运体3(EAAT3)表达导致大鼠吗啡复吸中的作用。方法:清洁级健康雄性SD大鼠32只，体重200～240 g，采用随机数字表法分为4组(n n＝8)：对照组(C组)、吗啡戒断组(E组)、吗啡复吸组(R组)和吗啡复吸＋干扰质粒组(RI组)。腹腔注射吗啡10 mg/kg，建立大鼠条件性位置偏爱(CPP)模型；停止给药使CPP逐渐消退；再次腹腔注射小剂量吗啡5 mg/kg诱导已消退的CPP恢复，记录伴药箱停留时间。CPP模型建立成功后RI组大鼠侧脑室注射μ-δ异源二聚体干扰质粒5 μl。采用高效液相色谱法测定海马谷氨酸含量，采用Western blot法检测海马内Nrf2和EAAT3的表达，采用RT-PCR法检测海马内Nrf2 mRNA的表达，采用蛋白免疫共沉淀法检测μ-δ异源二聚体与Nrf2相互作用情况。n 结果:与C组比较，R组和RI伴药箱停留时间延长，海马谷氨酸含量和μ-δ异源二聚体/Nrf2比值升高，E组和RI组海马Nrf2和EAAT3表达上调，E组、R组和RI组海马Nrf2 mRNA表达上调(n P<0.05)；与E组比较，R组和RI组伴药箱停留时间延长，海马谷氨酸含量和μ-δ异源二聚体/Nrf2比值升高，Nrf2和EAAT3表达下调(n P0.05)；与R组比较，RI组伴药箱停留时间缩短，海马谷氨酸含量和μ-δ异源二聚体/Nrf2比值降低，海马Nrf2和EAAT3表达上调(n P0.05)。n 结论:μ-δ异源二聚体形成后结合Nrf2，导致海马Nrf2含量减少，引起EAAT3表达下调，从而导致大鼠吗啡复吸的形成。“,”Objective:To evaluate the role of Nrf2 in morphine relapse caused by μ-δ heterodimer-induced down-regulation of excitatory amino acid transportor 3 (EAAT3) expression in rats.Methods:Thirty-two clean-grade healthy male Sprague-Dawley rats, weighing 200-240 g, were divided into 4 groups (n n = 8 each) using a random number table method: control group (group C), morphine withdrawal group (group E), morphine relapse group (group R), and morphine relapse plus interference plasmid group (group RI). Morphine 10 mg/kg was intraperitoneally injected to establish conditioned place preference (CPP) model; administration was stopped to make CPP gradually subside; a small dose of morphine 5 mg/kg was intraperitoneally injected again to induce the relapse of the subsided CPP, and the time spent in drug-paired box was recorded.In group RI, μ-δ heterodimer interference plasmid 5 μl was injected into the lateral ventricle after CPP model was successfully established.The content of glutamate in hippocampus was determined by high-performance liquid chromatography, and the expression of Nrf2 and EAAT3 was detected by Western blot, the expression of Nrf2 mRNA was detected by real-time polymerase chain reaction, and the interaction between μ-δ heterodimer and Nrf2 was detected by protein immunoprecipitation method.n Results:Compared with group C, the time spent in drug-paired box was significantly prolonged, and the glutamate content and μ-δ heterodimer/Nrf2 ratio were increased in R and RI groups, the expression of Nrf2 and EAAT3 was significantly up-regulated in E and RI groups, and the expression ofNrf2 mRNA was significantly up-regulated in E, R and RI groups ( n P0.05). Compared with group R, the time spent in drug-paired box was significantly shortened, the glutamate content and μ-δ heterodimer/Nrf2 ratio were decreased, the expression of Nrf2 and EAAT3 was up-regulated (n P0.05).n Conclusion:μ-δ heterodimer binds to Nrf2 after formation, leading to the decrease in hippocampal Nrf2 content, causing the down-regulation of EAAT3 expression, and thus resulting in the development of morphine relapse in rats.