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阿魏酸通过抑制 RhoA/p38MAPK 信号通路减轻坐骨神经痛的外周敏化。

Ferulic acid alleviates sciatica by inhibiting peripheral sensitization through the RhoA/p38MAPK signalling pathway.

机构信息

College of Traditional Chinese Medicine, Jinan University, Guangzhou, China.

College of Traditional Chinese Medicine, Jinan University, Guangzhou, China.

出版信息

Phytomedicine. 2022 Nov;106:154420. doi: 10.1016/j.phymed.2022.154420. Epub 2022 Aug 28.

DOI:10.1016/j.phymed.2022.154420
PMID:36115115
Abstract

BACKGROUND

Nonsteroidal anti-inflammatory drugs are used to relieve sciatica, but their effects are not satisfactory.

PURPOSE

This study aimed to explore the therapeutic effects of ferulic acid on sciatica.

METHODS

Thirty-two SD rats were randomly divided into 4 groups, i.e., sham operation group, chronic constriction injury (CCI) group, mecobalamin group, and ferulic acid group. We conducted behavioural tests, ELISA, PCR, Western blots, and immunofluorescence analysis. Specific inhibitors were used in cell experiments to explore the related mechanisms.

RESULTS

Thermal hyperalgesia was induced after CCI operation, and ferulic acid relieved thermal hyperalgesia. In addition, ferulic acid decreased the IL1β, IL6, TNF-α, and CRP mRNA levels; the IBA-1, iNOS, IL1β, RhoA, RhoA-GTP, COX2, Rock1, TRPV1, TRPA1, and p-p38MAPK levels in dorsal root ganglion (DRG) neurons; and the LPS, CRP, substance P (SP), and prostaglandin E2 (PGE2) levels in serum, and these levels were higher in the CCI group. In the cell experiments, LPS induced M1 polarization of GMI-R1 cells via the RhoA/Rock pathway. Ferulic acid attenuated LPS-induced M1 polarization by decreasing the levels of M1 polarization markers, including IL1β, IL6, TNF-α, iNOS, and CD32, and increased M2 polarization by increasing the levels of M2 polarization markers, including CD206 and Arg-1. LPS treatment clearly increased the iNOS, IL1β, RhoA, Rock1, Rock2 and p-p38 MAPK levels and reduced Arg-1 expression, and ferulic acid reversed these changes.

CONCLUSION

Ferulic acid can inhibit peripheral sensitization by reducing the levels of inflammatory factors, TRPA1 and TRPV1 through the RhoA/p38 MAPK pathway to alleviate sciatica.

摘要

背景

非甾体抗炎药被用于缓解坐骨神经痛,但疗效并不令人满意。

目的

本研究旨在探讨阿魏酸治疗坐骨神经痛的疗效。

方法

32 只 SD 大鼠随机分为 4 组,即假手术组、慢性压迫损伤(CCI)组、甲钴胺组和阿魏酸组。我们进行了行为学测试、ELISA、PCR、Western blot 和免疫荧光分析。在细胞实验中使用了特异性抑制剂来探讨相关机制。

结果

CCI 手术后大鼠出现热痛觉过敏,阿魏酸缓解了热痛觉过敏。此外,阿魏酸降低了白细胞介素 1β(IL1β)、白细胞介素 6(IL6)、肿瘤坏死因子-α(TNF-α)和 C 反应蛋白(CRP)mRNA 水平;背根神经节(DRG)神经元中的诱导型一氧化氮合酶(iNOS)、IL1β、小胶质细胞激活标志物(IBA-1)、RhoA、RhoA-GTP、环氧化酶 2(COX2)、Rock1、瞬时受体电位香草酸亚型 1(TRPV1)、瞬时受体电位锚蛋白亚型 1(TRPA1)和 p-p38MAPK 水平;以及血清中的脂多糖(LPS)、CRP、P 物质(SP)和前列腺素 E2(PGE2)水平,CCI 组这些水平均较高。在细胞实验中,LPS 通过 RhoA/Rock 通路诱导 GMI-R1 细胞发生 M1 极化。阿魏酸通过降低 M1 极化标志物(包括 IL1β、IL6、TNF-α和 iNOS)的水平并增加 M2 极化标志物(包括 CD206 和 Arg-1)的水平,减轻了 LPS 诱导的 M1 极化。LPS 处理明显增加了 iNOS、IL1β、RhoA、Rock1、Rock2 和 p-p38MAPK 水平并降低了 Arg-1 的表达,而阿魏酸则逆转了这些变化。

结论

阿魏酸通过 RhoA/p38MAPK 通路降低炎症因子、TRPA1 和 TRPV1 的水平,抑制外周敏化,从而缓解坐骨神经痛。

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