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目的:评价核因子E2相关因子2(Nrf2)/血红素氧合酶-1(HO-1)信号通路在右美托咪定减轻大鼠脓毒症相关性脑病中的作用。方法:清洁级健康成年雄性SD大鼠90只，3～4月龄，体重300～400 g，采用随机数字表法分为5组(n n＝18)：假手术组(Sham组)、脓毒症相关性脑病组(SAE组)、右美托咪定组(D组)、Nrf2抑制剂鸦胆子苦醇组(B组)和鸦胆子苦醇＋右美托咪定组(BD组)。采用盲肠结扎穿孔法(CLP)制备大鼠脓毒症相关性脑病模型，D组和BD组于造模前30 min时腹腔注射右美托咪定30 μg/kg，Sham组、SAE组和B组腹腔注射等容量生理盐水。B组和BD组于模型制备前10 d，隔天腹腔注射鸦胆子苦醇0.4 mg/kg。于CLP后24 h时处死大鼠取脑组织，观察病理学结果，计数存活神经元，计算神经元存活率，采用ELISA法测定TNF-α、IL-1β和IL-6含量，采用Western blot法测定Nrf2和HO-1的表达。n 结果:与Sham组比较，SAE组脑组织TNF-α、IL-1β和IL-6含量升高，Nrf2和HO-1表达上调，神经元存活率降低(n P<0.05)；与SAE组比较，D组脑组织TNF-α、IL-1β和IL-6含量降低，Nrf2和HO-1表达上调，神经元存活率升高(n P0.05)，神经元存活率升高(n P<0.05)；与D组比较，BD组脑组织TNF-α、IL-1β和IL-6含量升高，Nrf2和HO-1表达下调，神经元存活率降低(n P<0.05)。n 结论:Nrf2/HO-1信号通路参与了右美托咪定减轻大鼠脓毒症相关性脑病的过程。“,”Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (Nrf2/HO-1) signaling pathway in dexmedetomidine-induced reduction of sepsis-associated encephalopathy (SAE) in rats.Methods:Ninety clean-grade healthy male Sprague-Dawley rats, aged 3-4 months, weighing 300-400 g, were divided into 5 groups (n n=18 each) using a random number table method: sham operation group (group Sham), group SAE, dexmedetomidine group (group D), Nrf2 inhibitor brusatol group (group B), and brusatol plus dexmedetomidine group (group BD). The model of SAE was established by cecal ligation and puncture in anesthetized rats.Dexmedetomidine 30 μg/kg was intraperitoneally injected at 30 min before the model was established in D and BD groups , while the equal volume of normal saline was given instead in Sham, SAE and B groups.Nrf2 inhibitor brusatol 0.4 mg/kg was intraperitoneally injected every other day during 10 days before establishing the model in B and BD groups.The rats were sacrificed at 24 h after operation, and brain tissues were obtained for examination of the pathological changes and for determination of the number of viable neurons, contents of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) (by enzyme-linked immunosorbent assay), and expression of Nrf2 and HO-1 (by Western blot). The survival rate of neurons was calculated.n Results:Compared with group Sham, the contents of TNF-α, IL-1β and IL-6 were significantly increased, and the expression of Nrf2 and HO-1 was up-regulated, and the survival rate of neurons was decreased in group SAE (n P<0.05). Compared with group SAE, the contents of TNF-α, IL-1β and IL-6 were significantly decreased, and the expression of Nrf2 and HO-1 was up-regulated, and the survival rate of neurons was increased in group D (n P<0.05). Compared with group B, the contents of TNF-α, IL-1β and IL-6 were significantly decreased (n P0.05), and the survival rate of neurons was increased in group BD (n P<0.05). Compared with group D, the contents of TNF-α, IL-1β and IL-6 were significantly increased, the expression of Nrf2 and HO-1 was down-regulated, and the survival rate of neurons was decreased in group BD (n P<0.05).n Conclusion:Nrf2/HO-1 signaling pathway is involved in the process of dexmedetomidine-induced reduction of SAE in rats.