The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China; Department of Anesthesiology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.
Department of Anesthesiology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.
Eur J Pharmacol. 2021 Apr 15;897:173945. doi: 10.1016/j.ejphar.2021.173945. Epub 2021 Feb 14.
The objective of study was to investigate the inhibitory effect of sinomenine on neuropathic pain on dorsal root ganglia (DRG). The DRG cell line and spinal nerve ligation (SNL) model were used in this study. The effect of sinomenine on the cell viability was examined by MTT assay. The expression of p38 MAPK, NF-κB, c-fos, SP and TNF-α was detected by using immunofluorescence and immunohistochemistry assay. We also assessed the level of p-CaMKII, COX-2, p-CREB, IL-17A, TLR4 and IL-1β via western blotting and RT-qPCR. Compared to the controls, sinomenine showed a protective effect on TNF-α-induced apoptosis on DRG cells in a dose-dependent manner, with an increase of cell viability and a decrease of reactive oxygen species level as well as LDH release. Parallelly, sinomenine treatment significantly reduced the expression of various factors related to stress and inflammation, including p38 MAPK, NF-κB, c-fos, p-CAMKII, COX-2, p-CREB, TLR4 and IL-17A in DRG cells in vitro. Furthermore, we found that administration of sinomenine significantly reduced mechanical withdrawal threshold and thermal withdrawal latency and inhibited the inflammation and activation of p38 signaling in SNL rats. It is noting that combined therapy of sinomenine and pulsed radiofrequency exhibited higher efficacy of dorsal root ganglia inflammation than single treatment as well as the combination of oxycodone and pulsed radiofrequency. Sinomenine inhibited the apoptosis of DRG cell by regulating p38 MAPK/CREB signalling pathway, which provides evidence to alleviate neuropathic pain in clinic.
本研究旨在探讨青藤碱对背根神经节（DRG）神经病理性疼痛的抑制作用。本研究采用 DRG 细胞系和脊神经结扎（SNL）模型。通过 MTT 检测法检测青藤碱对细胞活力的影响。通过免疫荧光和免疫组织化学检测 p38MAPK、NF-κB、c-fos、SP 和 TNF-α的表达。我们还通过 Western blot 和 RT-qPCR 评估了 p-CaMKII、COX-2、p-CREB、IL-17A、TLR4 和 IL-1β的水平。与对照组相比，青藤碱在 TNF-α诱导的 DRG 细胞凋亡中表现出剂量依赖性的保护作用，细胞活力增加，活性氧水平和 LDH 释放减少。平行地，青藤碱处理显著降低了 DRG 细胞中与应激和炎症相关的各种因子的表达，包括 p38 MAPK、NF-κB、c-fos、p-CaMKII、COX-2、p-CREB、TLR4 和 IL-17A。此外，我们发现青藤碱给药显著降低了机械缩足阈值和热缩足潜伏期，并抑制了 SNL 大鼠的炎症和 p38 信号激活。值得注意的是，与单独治疗相比，青藤碱与脉冲射频联合治疗以及与羟考酮和脉冲射频联合治疗相比，对背根神经节炎症的疗效更高。青藤碱通过调节 p38 MAPK/CREB 信号通路抑制 DRG 细胞凋亡，为临床缓解神经病理性疼痛提供了依据。
