姜黄素对中脑定位注射脂多糖引起帕金森样病变小鼠的抗炎机制研究

Anti-inflammation mechanism of curcumin in mice with lipopolysaccharide-induced Parkinson's disease

目的免疫炎症被认为是帕金森病(Parkinson's disease,PD)的主要发病机制。前期研究发现姜黄素可改善由1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)造成的PD小鼠脑内胶质瘢痕的形成,提示其在神经系统可能具有神经保护作用。文中观察姜黄素对中脑注射脂多糖(lipopolysaccharide,LPS)引起的帕金森样病变模型小鼠的改善作用,初步探讨其作用机制。方法通过中脑定位注射LPS诱导炎性反应,模拟帕金森样病变,同时给予姜黄素进行治疗,7 d后通过转棍实验和悬挂实验对小鼠的运动能力进行评价;通过RT-PCR检测小鼠中脑内炎性因子肿瘤坏死因子(tumor nerosis factor,TNF)α和白细胞介素(iterleukin,IL)-1β的表达量,通过ELISA方法检测小鼠BV-2小胶质细胞系TNFα和IL-1β的释放量。通过免疫荧光和免疫印迹的方法检测核因子(nuclear factor,NF)-κB的核转位情况,通过双荧光素酶报告基因的方法检测NF-κB的转录活性。结果姜黄素可显著改善由LPS引起的小鼠运动障碍,降低脑内炎性因子TNFα和IL-1β的表达,减少TNFα和IL-1β的释放,可显著抑制NF-κB的核转位,降低NF-κB的转录活性。结论姜黄素可通过抑制NF-κB的核转位,降低NF-κB的转录活性来发挥抑制中脑炎症的作用,从而改善由于LPS引起的帕金森样病变炎症导致的小鼠运动障碍,这也为从天然产物中寻找PD的治疗药物提供线索。

Objective Inflammation plays an important role in Parkinson＇s disease. Previous study showed that curcumin could inhibit the formation of glia scar, indicating its protective effect on the central nervous system. This study aimed to investigate the effect of curcumin on Parkinson＇s disease induced by lipopolysaccharide （LPS） and its action mechanism. Methods We established a model of Parkinson＇s disease in mice by injection of LPS into the substantia nigra, and then treated them by oral administration of curcumin. After 7 days of medication, we evaluated the motor coordination of the mice by rota-rod test and hanging test, determined the expressions of TNFα and IL-1β by RT-PCR and their release from BV-2 cells by ELISA, observed the nuclear translocation of NFKB by immunofluorescence and Western blot, and detected the transcriptional activity of NFKB by dual-luciferase reporter gene as-say. Results Curcumin significantly attenuated LPS -induced dyskinesia and inhibited the inflammatory by decreasing the expressions and release of TNFα and IL-1β. It also suppressed the nuclear translocation and reduced the transcriptional activity of NFκB. Conclusion Curcumin can improve dyskinesia caused by LPS-induced Parkinson＇s disease in mice by inhibiting the nuclear transloca-tion and decreasing the transcriptional activity of NFκB, which has provided some evidence for the treatment of Parkinson＇s disease with natural products.