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目的：研究姜黄素诱导大鼠Kupffer 细胞Nrf2 核转位对脂多糖（LPS）引起的炎症细胞因子分泌的影响。方法：分别用10 μM、20 μM 和30 μM 干预Kupffer 细胞8 h，诱导Nrf2 核转位水平；将Kupffer 细胞随机分为对照组、LPS 组和干预组，对照组正常培养未加姜黄素和LPS，LPS 组用10μg/mL 的LPS 加入Kupffer 细胞培养液共同培养2 h；干预组用30 μM 姜黄素干预8h 后，余处理同LPS 组。Western blot 检测Nrf2 核转位水平，分光光度法检测细胞MDA、GSH 水平，ELISA 法检测上清液TNF-α 和 IL-6，放免法检测IL-1β。结果：①姜黄素诱导Kupffer 细胞Nrf2 核转位，核转位水平随浓度增加而增高。②LPS 组MDA 水平较对照组显著升高(P<0.01)，干预组MDA 水平较LPS 组显著降低(P<0.01)，仍显著高于对照组(P<0.01)。LPS 组GSH 水平较对照组显著降低(P<0.01)，干预组GSH 水平较LPS 组显著升高(P<0.01)，仍显著低于对照组(P<0.01)。③LPS 组上清液TNF-α, IL-1β 和 IL-6 显著高于对照组（P<0.01），干预组均显著低于模型组（P<0.01），但显著高于对照组（P<0.01）。结论：姜黄素通过诱导Kupffer 细胞Nrf2 核转位，降低LPS 诱导的氧化应激损伤，抑制Kupffer 细胞分泌炎症细胞因子。

英文摘要:

Objective: To investigate the effect of nuclear factor E2-related factor 2 (Nrf2) translocation induced by curcumine on lipopolysaccharide (LPS) mediated inflammatory cytokine expression in rat Kupffer cells. Methods: Kupffer cells were incubated in culture with 10 μM, 20 μM and 30 μM curcumine for 8 h to induce Nrf2 nuclear translocation. Kupffer cell was divided into control group, LPS and curcumine group. Cells in control group were incubated in culture only with RPMI 1640, cells in LPS group were treated with 10 μg/mL LPS for 2 h, cells in curcumine group were treated with 30 μM curcumine for 8 h and subsequently treated with 10 μg/mL LPS for 2 h. The Nrf2 in nuclear and cytoslic fraction was assayed by western blot analysis. The levels of MDA and GSH were measured by spectrophotometric method. The levels of TNF-α and IL-6 in culture medium were detected by the ELISA method, and the level of IL-1β was measured by radioimmunoassay. Results: ①The levels of Nrf2 in the nucleus increased markedly in Kupffer cells treated by different concentrations of curcumine compared with that of the cells in control group, and the level of nuclear Nrf2 increased with the concentration of curcumine. ②The level of MDA increased significantly in LPS group compared with that in the control group (P<0.01), which was significantly abrogated in curcumine group (P<0.01). Compared with that of the control group, the level of GSH decreased significantly in model group(P<0,01), the decreased GSH level in LPS group significantly abrogated in curcumine group (P<0.01). ③The levels of TNF-α, IL-1β and IL-6 in culture medium increased significantly in LPS group compared with that in control group（P<0.01）, the increased level was significantly abrogated in curcumine group (P<0.01). Conclusion: Curcumine can induce Nrf2 nuclear translocation in cultured Kupffer cells and decrease intercellular ROS, subsequently inhibit LPS-mediated inflammatory cytokine expression.

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