甲基莲心碱调节Gas6/Axl信号通路对带状疱疹后遗神经痛小鼠疼痛反应的影响

doi:10.3969/j.issn.1006-6233.2025.11.07

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摘要 目的: 探究甲基莲心碱(NEF)调节生长停滞特异性蛋白6(Gas6)/酪氨酸蛋白激酶受体(Axl)信号通路对带状疱疹后遗神经痛(PHN)小鼠疼痛反应的影响。方法: 构建PHN小鼠模型。建模成功的小鼠随机分成PHN组、NEF-L组(5mg/kg)、NEF-M组(10mg/kg)、NEF-H组(20mg/kg)、R428组(20mg/kg和125mg/kg Gas6/Axl信号通路抑制剂R428),NEF和R428均通过腹腔注射给药,每组各10只。另选取10只正常C57BL/6J小鼠作为对照组(NC组)。检测各组小鼠痛阈值及自发缩足反射次数;HE染色观察脊髓组织病理变化;ELISA检测小鼠脊髓组织炎症因子、前列腺素E2(PGE2)、5-羟色胺(5-HT)、P物质(SP)表达水平;TUNEL观察小鼠脊髓神经细胞凋亡;六胺银染色观察小鼠脊髓组织形态学改变;Western blot检测小鼠脊髓组织Gas6/Axl信号通路及凋亡相关蛋白表达。结果: PHN组小鼠脊髓组织及神经元纤维结构损伤严重,自发缩足反射次数、IL-6、IL-1β、PGE2、5-HT、SP、神经元凋亡率、Bax表达显著高于NC组(P<0.05),机械痛阈值、热痛阈值、Gas6、p-Axl/Axl、Bcl-2显著低于NC组(P<0.05);NEF-L组、NEF-M组、NEF-H组小鼠脊髓组织及神经元纤维结构损伤减轻,自发缩足反射次数、IL-6、IL-1β、PGE2、5-HT、SP、神经元凋亡率、Bax表达低于PHN组(P<0.05),机械痛阈值、热痛阈值、Gas6、p-Axl/Axl、Bcl-2高于PHN组(P<0.05);R428组小鼠脊髓组织及神经元纤维结构损伤加重,自发缩足反射次数、IL-6、IL-1β、PGE2、5-HT、SP、神经元凋亡率、Bax表达显著高于NEF-H组(P<0.05),机械痛阈值、热痛阈值、Gas6、p-Axl/Axl、Bcl-2显著低于NEF-H组(P<0.05)。结论: NEF能够改善PHN小鼠疼痛以及炎症反应,可能与激活Gas6/Axl信号通路密切相关。

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	雷剑
	黄丹
	葛兴森

关键词 ：带状疱疹后遗神经痛, 甲基莲心碱, 生长停滞特异性蛋白6/酪氨酸蛋白激酶受体信号通路, 疼痛反应

Abstract：Objective: To explore the effect of neferine (NEF) on pain response in postherpetic neuralgia (PHN) mice by regulating the growth arrest specific protein 6 (Gas6)/AXL receptor tyrosine kinase (Axl) signaling pathway. Methods: PHN mice models were constructed. The successfully modeled mice were stochastically separated into PHN group, NEF-L group (5mg/kg), NEF-M group (10mg/kg), NEF-H group (20mg/kg), R428 group (20mg/kg and 125mg/kg Gas6/Axl signaling pathway inhibitor R428). Both NEF and R428 were administered via intraperitoneal injection, each with 10 mice. Another 10 normal C57BL/6J mice were served as the control group (NC group). The pain threshold and spontaneous foot contraction reflex frequency of mice were measured. HE staining was used to observe pathological changes in spinal cord tissue. ELISA was used to measure the inflammatory factors, prostaglandin E2 (PGE2), 5-hydroxytryptamine (5-HT), and substance P (SP) in mouse spinal cord tissue. TUNEL was used to observe apoptosis of spinal cord neurons in mice. Hexamine silver staining was used to observe morphological changes in mouse spinal cord tissue. Western blot was used to measure the Gas6/Axl signaling pathway and apoptosis related proteins in mouse spinal cord tissue. Results: The PHN group showed severe damage to the spinal cord tissue and neuronal fiber structure in mice, conspicuously higher spontaneous foot contraction reflex frequency, IL-6, IL-1β, PGE2, 5-HT, SP, neuronal apoptosis rate, Bax (P<0.05), and conspicuously lower mechanical pain threshold, thermal pain threshold, Gas6, p-Axl/Axl, Bcl-2 than the NC group (P<0.05). The NEF-L group, NEF-M group, and NEF-H group showed reduced damage to the spinal cord tissue and neuronal fiber structure in mice, lower spontaneous foot contraction reflex frequency, IL-6, IL-1β, PGE2, 5-HT, SP, neuronal apoptosis rate, Bax (P<0.05), and higher mechanical pain threshold, thermal pain threshold, Gas6, p-Axl/Axl, Bcl-2 than the PHN group (P<0.05). The R428 group showed aggravated damage to spinal cord tissue and neuronal fiber structure in mice, conspicuously higher spontaneous foot contraction reflex frequency, IL-6, IL-1β, PGE2, 5-HT, SP, neuronal apoptosis rate, Bax (P<0.05), and conspicuously lower mechanical pain threshold, thermal pain threshold, Gas6, p-Axl/Axl, Bcl-2 than the NEF-H group (P<0.05). Conclusion: NEF can improve pain and inflammatory response in PHN mice, which may be closely related to the activation of Gas6/Axl signaling pathway.

Key words： Postherpetic neuralgia Neferine Growth arrest specific gene 6/AXL receptor tyrosine kinase signaling pathway Pain response

基金资助:中国中医科学院广安门医院南区院级课题,(编号:Y2023-01)

引用本文:

雷剑, 黄丹, 葛兴森. 甲基莲心碱调节Gas6/Axl信号通路对带状疱疹后遗神经痛小鼠疼痛反应的影响[J]. 河北医学, 2025, 31(11): 1801-1807.
LEI Jian, HUANG Dan, GE Xingsen. The Effect of Neferine on Pain Response in Postherpetic Neuralgia Mice by Regulating the Gas6/Axl Signaling Pathway. HeBei Med, 2025, 31(11): 1801-1807.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.11.07 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I11/1801

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