Rhynchophyllin attenuates neuroinflammation in Tourette syndrome rats via JAK2/STAT3 and NF-κB pathways

Rhynchophyllin attenuates neuroinflammation in Tourette syndrome rats via JAK2/STAT3 and NF-κB pathways
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钩藤碱通过 JAK2/STAT3 和 NF-κB 通路减轻抽动秽语综合征大鼠的神经炎症

DOI:
10.1002/tox.22813
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发表时间:
2019-10-01
影响因子:
4.5
通讯作者:
Huang Yaruo
Huang Yaruo
中科院分区:
医学3区
文献类型:
--
作者:
Long Hongyan;Zhang Mengjiao;Huang Yaruo

文献摘要

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本研究旨在探讨钩藤碱(RH)对多发性抽动症(TS)大鼠神经炎症的影响。采用选择性5-HT2A/2C激动剂1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷(DOI)建立大鼠TS模型。对DOI诱导的大鼠进行行为学测试。检测血清和纹状体中白介素1β(IL-1β)、白介素6(IL-6)、肿瘤坏死因子-α(TNF-α)等炎性细胞因子水平。用Western印迹法检测JAK2/信号转导和转录激活因子3(STAT3)及核因子-kappaB通路在纹状体的表达水平。结果表明,RH能显著减少TS大鼠的点头实验次数。免疫组织化学和Western印迹分析显示,RH可显著降低TS大鼠血清和纹状体中IL-6、IL-1β和TNF-α的表达,并改变其P-JAK2、P-STAT3、P-NF-kappaBp65和P-I kappa Bα的表达,提示RH对TS的作用机制可能与调节JAK2/STAT3和NF-kappa B通路有关。
The aim of this study was designed to investigate the effects of rhynchophyllin (RH) on neuroinflammation in Tourette syndrome (TS) rats. TS model was established in rats by the injection of selective 5-HT2A/2C agonist 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Behavior in DOI-induced rats was tested. Inflammatory cytokines levels such as interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in serum and striatum were detected. The expression levels of janus kinase 2 (JAK2)/signal transducer and transcription activator 3 (STAT3) and nuclear factor (NF)-kappa B pathways in striatum were measured by Western blot. Data indicated that RH can significantly reduce the numbers of nodding experiment of TS rats. RH significantly decreased IL-6, IL-1 beta, and TNF-alpha in serum and striatum of TS rats, with altered expression of P-JAK2, P-STAT3, P-NF-kappa Bp65, and P-I kappa B alpha in TS rats, as evidenced by Western blot analysis and immunohistochemistry, suggesting that the regulation of JAK2/STAT3 and NF-kappa B pathways might be involved in the mechanism of RH on TS.