阿魏酸钠抑制Aβ_(25-35)激活小鼠巨噬细胞引起的神经细胞损伤

Sodium ferulate inhibits neurons injury mediated by Aβ_(25-35)-induced macrophage activation of mice

目的探讨阿魏酸钠(SF)抑制淀粉样β蛋白(Aβ25-35)激活巨噬细胞引起的神经细胞损伤及其机制。方法单独培养小鼠腹腔巨噬细胞以及与神经细胞联合培养,加入10μmol/L的Aβ25-35,保护组加入不同浓度的SF。单独培养的巨噬细胞,采用Western blot和ELISA法分析P38 MAPK水平和检测肿瘤坏死因子-α(TNF-α)生成量。神经细胞和巨噬细胞联合培养,采用免疫组织化学方法和LDH检测试剂盒检测微管相关蛋白2(MAP-2)的表达水平和乳酸脱氢酶(LDH)漏出量。结果SF能显著降低Aβ25-35诱导的腹腔巨噬细胞核蛋白P38 MAPK的含量及细胞的TNF-α水平,能显著地降低LDH漏出量,使MAP-2表达水平明显增加,呈剂量依赖性(P<0.05)。结论SF可抑制Aβ25-35诱导的P38 MAPK通路,使TNF-α水平降低,对神经细胞具有保护作用。

Objective To examine the effect and mechanism of sodium ferulate inhibiting P38 MAPK in macrophage on neurotoxicity which was mediated by fribrilar-amyloid-induced. Methods The isolated peritoneal macropohages were cultured. P38 MAPK protein in nuclear extracts was analyzed by Western blot and production of tumor necrosis factor-α （TNF-α） was detected by ELISA. For neuron-macrophage co-cultures, Microtubute-associated protein-2 （MAP-2） expression was detected by immunocytochemical technique. The level of LDH in the medium was measured. Results The production of TNF-α and P38 MAPK protein in nuclear extracts increased signifi cantly by incubation with Aβ25-35. LDH efflux in neuron-macrophage co-culture medium increased and MAP-2 expression decreased significantly（P 〈 0.01 ）. As to the sodium ferulate groups, however, the damages were eliminated in a dose-dependent manner （P 〈 0.05 ）. Conclusion Sodium ferulate could inhibit P38 MAPK mediated by Aβ25-35 and decrease the production of TNF-α. Sodium ferulate could play a role in protecting the neurons against the impairments induced by Aβ25-35.