为研究内毒素耐受对核苷酸结合寡聚化结构域2(nucleotide­-binding oligomerization domain containing 2，NOD2)信号通路的影响，将小鼠单核-­巨噬细胞RAW264.7分为两组，分别给予小剂量脂多糖(lipopolysaccharide，LPS)(100 ng/mL)或磷酸盐缓冲液(phosphate buffered saline，PBS)预处理20 h，建立内毒素耐受组和对照组。每组细胞分别给予大剂量LPS(1 000 ng/mL)或热灭活烟曲霉孢子刺激，于刺激后0、2、6、12、24 h采用定量聚合酶链反应(polymerase chain reaction，PCR)检测细胞NOD2、受体相互作用蛋白2(recepto-r­interacting protein 2，RIP2)和肿瘤坏死因子α(tumor necrosis factor α，TNF-­α)mRNA表达；采用酶联免疫吸附试验(enzyme-­linked immunosorbent assay，ELISA)检测细胞上清液中白细胞介素8(interleukin 8，IL­-8)和TNF-­α浓度。结果显示，内毒素耐受组无论是大剂量LPS还是热灭活烟曲霉孢子刺激均不能增加NOD2、RIP2 和TNF­-α mRNA表达及细胞上清液中IL-­8、TNF­-α浓度；而对照组大剂量LPS和热灭活烟曲霉孢子刺激均可提高NOD2、RIP2 和TNF-­α mRNA表达及细胞上清液中IL-­8、TNF­-α浓度，尤以刺激后12 h增加显著，与刺激前(0 h)比较，差异有统计学意义(P＜0.05)。结果提示，内毒素耐受可能对NOD2信号通路有抑制作用。

To investigate the potential effect of endotoxin tolerance on nucleotide­-binding oligomerization domain containing 2 (NOD2) signaling pathway, murine macrophage RAW264.7 cells were pretreated with lipopolysaccharide (LPS, 100 ng/mL) or phosphate buffered saline (PBS) for 20 h to establish endotoxin tolerance group and control group respectively. Both groups were subjected to the treatment with LPS (1 000 ng/mL) or heat­killed Aspergillus fumigatus (HAf). The mRNA levels of NOD2, receptor-­interacting protein 2 (RIP2) and tumor necrosis factor α (TNF-­α) were measured at 0, 2, 6, 12, 24 h after stimulation by real-­time quantitative polymerase chain reaction (PCR). The concentrations of secreted TNF-­α and interleukin 8 (IL­-8) were also quantified by enzyme-­linked immunosorbent assay (ELISA). The collective results showed that neither LPS nor HAf had any significant effect on NOD2, RIP2, and TNF­-α transcription or TNF­-α and IL­-8 secretion in the endotoxin tolerance group. On the contrary, a clear up-­regulation was detected in the control group upon either LPS or HAf treatment, concomitant with a peak at 12 h after stimulation. These data indicate that the NOD2 signaling pathway might be suppressed under endotoxin tolerance conditions.