目的 探讨粒细胞集落刺激因子（G-CSF）对阿尔茨海默病（AD）大鼠认知障碍的改善作用及其对脑内炎症反应的影响。 方法 45只雄性SD大鼠，随机分为3组，包括假手术组、模型组、G-CSF组，每组15只。采用β-淀粉样蛋白1-42（Aβ _1-42）复制AD大鼠模型，并给予G-CSF治疗。观察并比较大鼠的学习记忆功能及脑组织病理学变化。采用Western blotting检测核因子κB p65（NF-κB p65）、磷酸化p-38丝裂原活化蛋白激酶（p-p38MAPK）、诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）、肿瘤坏死因子α（TNF-α）和白细胞介素-1β（IL-1β）蛋白的表达，采用Real-time PCR检测iNOS、COX-2、TNF-α和 IL-1β mRNA水平。结果 模型组大鼠神经细胞数量明显减少，细胞核固缩明显，核仁不清。G-CSF组大鼠脑组织神经细胞核固缩现象均有显著改善。假手术组、模型组、G-CSF组逃避潜伏期分别为（35.68±6.73）s、（57.92±7.35）s及（40.27±8.91）s；目标象限游泳时间分别为54.72%±4.22%、36.73%±3.21%及44.68%±4.01%；穿过平台次数分别为（8.7±2.1）次、（3.9±1.6）次及（6.5±1.7）次；与模型组相比，假手术组、G-CSF组的逃避潜伏期均显著缩短，目标象限游泳时间显著增加，穿过平台次数显著增加，差异均有统计学意义（P<0.05）。假手术组、模型组、G-CSF组NF-κB p65蛋白表达水平为.144±0.033、0.502±0.035及0.473±0.061；p-p38 MAPK蛋白水平为0.194±0.021、0.511±0.039及0.266±0.048，与模型组相比，假手术组、G-CSF组NF-κB p65、p-p38MAPK蛋白水平均显著降低，差异均有统计学意义（P<0.05）。与模型组比较，假手术组、G-CSF组iNOS、COX-2、TNF-α 和 IL-1β的蛋白和mRNA 水平显著降低（P<0.05）。 结论 G-CSF具有良好的抑制AD模型大鼠脑神经细胞凋亡，改善大鼠学习记忆功能障碍的作用，其作用可能通过抑制p38MAPK和NF-κB p65的信号通路的过度激活，下调iNOS、COX-2、TNF-α 和 IL-1β等炎性因子的表达，抑制脑内神经炎症状态而实现。

Objective To investigate the effect of granulocyte colony-stimulating factor (G-CSF) on cognitive impairment in Alzheimer’s disease(AD) in rats and its effect on brain inflammatory response. Methods Forty-five male Sprague-Dawley rats were randomly divided into 3 groups: sham operation group, model group, and G-CSF group. Rat models were induced by intracerebro ventricular injection of amyloid beta-peptides 1-42 (Aβ_1-42), and then G-CSF were given to G-CSF group. The learning and memory function and brain histopathological changes were observed and compared. The expression of nuclear factor κB p65 (NF-κB p65), phosphorylated p38 mitogen activated protein kinase (p-p38MAPK), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor α(TNF-α) and interleukin-1β(IL-1β) were detected by Western blotting. The levels of iNOS, COX-2, TNF-α and IL-1β mRNA were detected by Real-time PCR. Results The number of neurons in the model group decreased significantly, the nuclear condensation was obvious and the nucleolus was unclear. Neuronal nuclear condensation was significantly improved in G-CSF group. The escape latency of the sham group, model group and G-CSF group were (35.68±6.73) s, (57.92±7.35) s and (40.27±8.91)s. The swimming time of the target quadrant was 54.72%±4.22%, 36.73%±3.2% and 44.68%±4.01%. The times of crossing the platform were 8.7±2.1, 3.9±1.6 and 6.5±1.7. Compared with the model group and the control group, the escape latency of G-CSF group were significantly shorter, target quadrant swimming time increased significantly, through the platform number increased significantly, the difference had statistical significance (P<0.05).In the sham group, model group and G-CSF group, the protein levels of NF-κB p65 were 0.144±0.033, 0.502±0.035 and 0.473±0.061, the protein levels of p-p38MAPK were 0.194±0.021, 0.511±0.039 and 0.266±0.048. Compared with the model group, the levels of F-κB p65 and p-p38MAPK protein in the sham group and G-CSF group decreased significantly, and the difference was statistically significant(P<0.05). Compared with the model group, the protein and mRNA levels of iNOS, COX-2, TNF-α and IL-1β in the sham group and G-CSF group were significantly lower than those in the model group (P<0.05).Conclusion G-CSF can improve the learning and memory dysfunction of rats with Alzheimer’s disease probably through inhibiting the activation of p38 MAPK and NF-κB p65 signaling pathways and down-regulating iNOS, COX-2, TNF-α and IL-1β expressions to inhibit the neuroinflammatory state of the brain.