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电针通过TLR2/4-MyD88-NF-κB通路对吗啡诱导的瘙痒模型小鼠的止痒作用。

Antipruritic effects of electroacupuncture on morphine-induced pruritus model mice through the TLR2/4-MyD88-NF-κB pathway.

作者信息

Ye Yu Shan, Pan Ai Zhen, Zhen Yan, Kang Meng Ru, Zhang Bin, Yi Wei Min

机构信息

Departments of Stomatology.

Integrative Medicine.

出版信息

Neuroreport. 2019 Mar 20;30(5):331-337. doi: 10.1097/WNR.0000000000001203.

Abstract

Pruritus is one of the common side effects of intrathecal or epidural injection of opioids. The aim of this study was to test the antipruritic effect of acupuncture and its possible mechanism. We used electroacupuncture (EA), toll-like receptor (TLR)2/4 antagonist sparstolonin B (SsnB), and TLR2/4 agonist peptidoglycan (PGN) to precondition female wild-type BALB/c mice, and then prepared a morphine-induced pruritus model. The mRNA and protein expression levels of TLR2, TLR4, MyD88, and NF-κB were detected by RT-PCR and western blotting. The contents of interleukin (IL)-1, IL-6, IL-12, IL-10, and tumor necrosis factor-α in serum were measured by ELISA assays. Flow cytometry was performed to analyze the ratio of M1-phenotype to M2-phenotype macrophages. Our results showed that EA preconditioning improved pruritus; reduced the expressions of TLR2, TLR4, MyD88, and NF-κB both at the mRNA and protein levels (P<0.05); reduced the expression of proinflammatory cytokines IL-1, IL-6, IL-12, and tumor necrosis factor-α; and increased the expression of anti-inflammatory cytokine IL-10 (P<0.05). EA promoted M2-phenotype macrophage differentiation. Moreover, these results showed no significant difference between the SsnB group and the EA+SsnB group (P>0.05), but showed a significant difference between the PGN group and the EA+PGN group (P<0.05). Therefore, we propose that EA may be involved in the remission of pruritus in morphine-induced pruritus model mice through the TLR2/4-MyD88-NF-κB pathway. EA is a potential therapeutic treatment for pruritus.

摘要

瘙痒是鞘内或硬膜外注射阿片类药物常见的副作用之一。本研究旨在测试针刺的止痒作用及其可能机制。我们采用电针(EA)、Toll样受体(TLR)2/4拮抗剂蛇床子素B(SsnB)和TLR2/4激动剂肽聚糖(PGN)对雌性野生型BALB/c小鼠进行预处理,然后制备吗啡诱导的瘙痒模型。通过逆转录聚合酶链反应(RT-PCR)和蛋白质印迹法检测TLR2、TLR4、髓样分化因子88(MyD88)和核因子κB(NF-κB)的mRNA和蛋白表达水平。采用酶联免疫吸附测定(ELISA)法检测血清中白细胞介素(IL)-1、IL-6、IL-12、IL-10和肿瘤坏死因子-α的含量。通过流式细胞术分析M1型与M2型巨噬细胞的比例。我们的结果显示,EA预处理可改善瘙痒;在mRNA和蛋白水平上降低TLR2、TLR4、MyD88和NF-κB的表达(P<0.05);降低促炎细胞因子IL-1、IL-6、IL-12和肿瘤坏死因子-α的表达;增加抗炎细胞因子IL-10的表达(P<0.05)。EA促进M2型巨噬细胞分化。此外,这些结果显示SsnB组与EA+SsnB组之间无显著差异(P>0.05),但PGN组与EA+PGN组之间存在显著差异(P<0.05)。因此,我们认为EA可能通过TLR2/4-MyD88-NF-κB途径参与吗啡诱导的瘙痒模型小鼠瘙痒的缓解。EA是一种潜在的瘙痒治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d3/6410968/848303237567/wnr-30-331-g001.jpg

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