目的 探讨蛋白激酶R样内质网激酶 (PERK) 介导的内质网应激通路在脂多糖（LPS）诱导的小胶质细胞炎症模型中的作用。方法  通过梯度浓度 LPS 刺激 24 h和1 mg/L LPS 刺激不同时间构建小胶质细胞炎症模型，探究其对内质网应激的影响。利用CCK-8实验检测细胞活力；Real-time PCR及ELISA试剂盒检测相关炎症因子的mRNA及蛋白表达水平；细胞活性氧(ROS)检测细胞氧化应激水平；Real-time PCR及Western blotting检测炎症相关指标和内质网应激通路相关指标的mRNA及蛋白的表达水平。结果  1. 不同浓度的LPS作用BV-2细胞24 h后对细胞活力及形态的影响差别无统计学意义（P>0.05）；2. 1 mg/L LPS与BV-2细胞孵育不同的时间，细胞活力随着时间的增加而降低；3. 与0 h组相比，LPS刺激9、12和24 h组中促炎细胞因子白细胞介素 (IL)-1β、肿瘤坏死因子α (TNF-α) 的mRNA及蛋白表达水平均显著上升（P<0.05），成功建立炎症模型；4. 与0 h组相比，LPS刺激9、12和24 h组，内质网应激通路相关指标的蛋白及mRNA表达水平显著上升（P<0.01），呈现时间依赖性；5. 加入PERK抑制剂GSK2606414后，与LPS组相比，PERK抑制剂组内质网应激相关指标的mRNA及蛋白表达水平显著降低（P<0.05）； 6. 与LPS组相比，PERK抑制剂组促炎细胞因子的mRNA及蛋白表达水平及ROS荧光强度显著下降（P<0.01）。结论  靶向PERK介导的内质网应激可抑制LPS诱导的小胶质细胞炎症反应。

Objective To explore the role of the protein kinase R-like endoplasmic reticulum kinase (PERK)-mediated endoplasmic reticulum stress pathway in a model of lipopolysaccharide(LPS)-induced microglia inflammation.   Methods  To investigate its effects on endoplasmic reticulum (ER) stress, an inflammation model of microglia was established by stimulating with LPS at gradient concentrations for 24 hours and with 1 mg/L LPS for different durations. Cell viability was assessed by the CCK-8 assay; The mRNA and protein expression levels of related inflammatory factors were measured by Real-time PCR and ELISA kits. Cellular oxidative stress was evaluated by detecting reactive oxygen species (ROS), and Realtime PCR and Western blotting were used to examine the mRNA and protein expression levels of ER stress pathway markers associated with inflammation.   Results  1. The effects of different concentrations of LPS on cell viability and morphology were not statistically significant after acting on BV-2 cells for 24 hours (P>0.05); 2. 1 mg/L LPS incubated with BV-2 cells for different times and the cell viability decreased with the increase of time; 3. Compared with the 0 hour group, the levels of pro-inflammatory cytokine interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) mRNA and protein expression increased significantly (P<0.05) in the LPS-stimulated 9 hours, 12 hours, and 24 hours groups, and the inflammation model was successfully established; 4. Compared with the 0 hour group, the protein and mRNA expression levels of the endoplasmic reticulum stress pathway-related indexes in the LPS-stimulated 9 hours, 12 hours, and 24 hours groups increased significantly (P<0.01), which showed the time-dependence; 5. After adding the PERK inhibitor GSK2606414, the mRNA and protein expression levels of endoplasmic reticulum stress-related indicators in the PERK inhibitor group were significantly reduced compared with those in the LPS group (P<0.05); 6. The mRNA and protein expression levels of pro-inflammatory cytokines and the fluorescence intensity of ROS in the PERK inhibitor group were significantly reduced compared with those in the LPS group (P<0.01). Conclusion  Targeting PERK-mediated endoplasmic reticulum stress inhibits LPS-induced inflammatory responses in microglia.