芍药苷通过抑制脊髓Akt-NF-kB信号通路及小胶质细胞激活缓解炎症性疼痛

Paeoniflorin Attenuates Inflammatory Pain via Blocking Akt-NF-κB Signaling and Activation of Microglia in the Spinal Cord

芍药苷具有抑制炎症和镇痛的作用,在治疗炎症疼痛方面具有重要价值,但其作用机制尚不明确。本研究发现,弗氏完全佐剂诱导小鼠炎症疼痛模型,用80 mg/kg芍药苷腹腔注射能有效缓解疼痛。检测发现芍药苷治疗后,小鼠机械性痛阈与热板痛阈均明显升高(机械性痛阈值:由6.38±1.00 g提高至8.31±0.81 g;热板痛阈值:由5.78±0.76 s提高至9.90±1.58 s);同时抑制外周炎症因子TNF-α等的释放(由708.71±46.55 pg/m L降低至588.65±16.02 pg/m L);免疫组织化学检测发现,芍药苷能有效抑制脊髓背角小胶质细胞的激活;NO检测结果发现,脊髓部位NO合成降低(3.55±0.28μmol/L·g-1Pro降至2.25±0.71μmol/L·g-1Pro);Western印迹检测证实,脊髓部位i NOS在使用芍药苷后,表达恢复正常水平。同时发现,Akt-NF-κB信号可能参与芍药苷的镇痛作用。上述结果提示,芍药苷缓解慢性炎症疼痛可通过抑制炎症因子释放,也通过抑制脊髓小胶质细胞的激活,而此过程依赖抑制Akt-NF-κB信号的激活。

Anti-inflammatory and paregoric effects of paeoniflorin（ PF） had great medical value in analgesia. This study aims to clarify the effect of PF on inflammation-induce pain,and its potential molecular mechanism. ICR mice intraplantar injected with 20 μL Freund＇s adjuvant incomplete（ CFA）were used as inflammatory pain models. PF attenuated mechanical and thermal pain scores（ MPWT： Sham12. 43 ± 1. 04 g,CFA 6. 38 ± 1. 00 g,CFA ＋ PF 8. 31 ± 0. 81 g; TPWT： Sham 14. 60 ± 1. 80 s,CFA 5. 78± 0. 76 s,CFA ＋ PF 9. 90 ± 1. 58 s）,and inhibited the production of TNF-α（ TNF-α： Sham 523. 84 ±57. 59 pg/m L,CFA 708. 71 ± 46. 55 pg/m L,CFA ＋ PF 588. 65 ± 16. 02 pg/m L）. The activation of microglia and NO production was inhibited by PF. Western blotting results showed that i NOS decreased after PF treatment,which was involved in the Akt-NF-κB signaling pathway. These results suggested that PF could efficiently attenuate inflammatory pain in vivo,and inhibited the increase of pro-inflammatory factors,the activation of microglia in the spinal cord,which was dependent on inhibiting the Akt-NF-κB signaling pathway.