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厚朴酚在小鼠神经性疼痛模型中的镇痛作用

Antinociceptive Effect of Magnolol in a Neuropathic Pain Model of Mouse.

作者信息

Zhang Xiao, Wang Juntao, Sui Aihua, Zhang Nannan, Lv Qiulan, Liu Zhenfang

机构信息

Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People's Republic of China.

Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People's Republic of China.

出版信息

J Pain Res. 2021 Jul 8;14:2083-2093. doi: 10.2147/JPR.S317204. eCollection 2021.

Abstract

BACKGROUND AND OBJECTIVE

Neuropathic pain remains a clinical challenge with limited effective treatments. Previous studies have found that magnolol (Mag), an ingredient existing in some herbs, showed neuroprotective effect. However, it remains unclear whether Mag can alleviate neuropathic pain.

METHODS

Chronic constriction injury (CCI) is used as the neuropathic pain model. Mice were randomly divided into 5 groups: Sham, CCI, CCI + 5, 10, 30 mg/kg Mag groups. Thermal and mechanical paw withdrawal threshold were performed at baseline and on the 3rd, 5th, 7th, 14th days post-surgery. Lumbar spinal cord and blood samples were collected on the 14th day. Blood lipid profile, kidney and liver functions, as well as the activation of microglia were evaluated, along with the related signal pathway examined using multiple methods including immunohistochemistry, RT-PCR and Western blot.

RESULTS

Mag alleviated thermal and mechanical hypersensitivity in CCI mice. CCI activated microglia and upregulated the expression of P2Y12, while Mag inhibited microglial activation, and downregulated the expression of P2Y12. Mag also blocked the activation of p38 mitogen-activated protein kinase (MAPK) and other pain-related cytokines such as IL-6, TNF-α and IL-1β.

CONCLUSION

The findings indicate that Mag has antinociceptive effect on neuropathic pain, probably mediated through P2Y12 receptors and p38 MAPK mediated pathways. With its relatively safe profile, Mag may be a potential therapeutic agent for neuropathic pain.

摘要

背景与目的

神经性疼痛仍然是一个临床挑战,有效治疗方法有限。先前的研究发现,厚朴酚(Mag),一种存在于某些草药中的成分,具有神经保护作用。然而,Mag是否能减轻神经性疼痛仍不清楚。

方法

采用慢性缩窄损伤(CCI)作为神经性疼痛模型。将小鼠随机分为5组:假手术组、CCI组、CCI + 5、10、30 mg/kg Mag组。在基线以及术后第3、5、7、14天进行热刺激和机械性爪撤离阈值测试。在第14天收集腰段脊髓和血液样本。评估血脂谱、肝肾功能以及小胶质细胞的激活情况,并使用免疫组织化学、RT-PCR和蛋白质免疫印迹等多种方法检测相关信号通路。

结果

Mag减轻了CCI小鼠的热刺激和机械性超敏反应。CCI激活了小胶质细胞并上调了P2Y12的表达,而Mag抑制了小胶质细胞的激活,并下调了P2Y12的表达。Mag还阻断了p38丝裂原活化蛋白激酶(MAPK)以及其他疼痛相关细胞因子如IL-6、TNF-α和IL-1β的激活。

结论

研究结果表明,Mag对神经性疼痛具有镇痛作用,可能是通过P2Y12受体和p38 MAPK介导的途径实现的。由于其相对安全的特性,Mag可能是一种治疗神经性疼痛的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928f/8275150/d625dff13777/JPR-14-2083-g0001.jpg

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