黄芪桂枝五物汤通过 TNFα/IL-1β/IL-6/MAPK/NF-κB 通路防治奥沙利铂所致神经病理性疼痛。

Huangqi Guizhi Wuwu Decoction can prevent and treat oxaliplatin-induced neuropathic pain by TNFα/IL-1β/IL-6/MAPK/NF-kB pathway.

机构信息

Department of Integrated Traditional Chinese and Western Medicine Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, P.R. China.

Liaoning University of Traditional Chinese Medicine, Shenyang 110085, Liaoning Province, P.R. China.

出版信息

Aging (Albany NY). 2022 Jun 27;14(12):5013-5022. doi: 10.18632/aging.203794.

OBJECTIVE

This study explored the effects and mechanisms of Huangqi Guizhi Wuwu Decoction on chemotherapy-induced neuropathic pain (CINP).

METHODS

Bodyweight and related behavioral testing of the rat model were utilized to investigate the effects of Huangqi Guizhi Wuwu Decoction on CINP. ELISA was used to measure the levels of TNF-α, IL-1β, and IL-6, in the serum of chronic CINP rats. Immunohistochemistry and Western blot analysis were performed to detect the expression of MAPK pathway related-proteins namely ERK1/2, p38, and JNK, and the expression of downstream essential proteins such as c-Fos, CREB, and NF-κB.

RESULTS

Body weight and related behavioral testing of the rat model suggests that Huangqi Guizhi Wuwu Decoction can improve the slow weight gain of oxaliplatin-induced chronic CINP model rats and effectively prevent and treat oxaliplatin-induced regular CIPN rat model of hyperalgesia. It can also oppress the mechanical pain threshold, cold pain threshold, and heat pain threshold decreased. Furthermore, by ELISA, immunohistochemistry, and western blot analysis, we found that Huangqi Guizhi Wuwu Decoction can down-regulate the levels of TNF-α, IL-1β, and IL-6 in the serum of chronic CINP rats induced by oxaliplatin. It also suppresses the expression of MAPK pathway related-proteins ERK1/2, p38, and JNK. This results in a decrease in the expression of downstream essential proteins, c-Fos, CREB, and Nf-κB.

CONCLUSIONS

In conclusion, we found that Huangqi Guizhi Wuwu Decoction can combat nerve cell injury, reduce pain sensitization, and prevent and repair the damage of nerve cells in the oxaliplatin CINP model rats via TNFα/IL-1β/IL-6/MAPK/NF-kB pathway.

目的

本研究探讨了黄芪桂枝五物汤对化疗诱导性神经病理性疼痛（CINP）的作用及机制。

方法

采用大鼠模型的体重及相关行为测试，观察黄芪桂枝五物汤对 CINP 的作用。采用酶联免疫吸附试验（ELISA）测定慢性 CINP 大鼠血清中 TNF-α、IL-1β 和 IL-6 的水平。采用免疫组织化学和 Western blot 分析检测 MAPK 通路相关蛋白 ERK1/2、p38 和 JNK 的表达以及下游必需蛋白 c-Fos、CREB 和 NF-κB 的表达。

结果

大鼠模型的体重及相关行为测试表明，黄芪桂枝五物汤可改善奥沙利铂诱导的慢性 CINP 模型大鼠体重增长缓慢，有效防治奥沙利铂诱导的 CIPN 大鼠模型痛觉过敏，还能抑制机械痛阈、冷痛阈和热痛阈降低。此外，通过 ELISA、免疫组化和 Western blot 分析发现，黄芪桂枝五物汤可下调奥沙利铂诱导的慢性 CINP 大鼠血清中 TNF-α、IL-1β 和 IL-6 的水平，抑制 MAPK 通路相关蛋白 ERK1/2、p38 和 JNK 的表达，从而降低下游必需蛋白 c-Fos、CREB 和 NF-κB 的表达。