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钩藤碱通过 BDNF/NF-κB 通路体内和体外减轻抽动秽语综合征。

Rhynchophylline Attenuates Tourette Syndrome via BDNF/NF-κB Pathway In Vivo and In Vitro.

机构信息

Central Laboratory, Nanjing Hospital of Chinese Medicine, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210001, China.

Nanjing University of Chinese Medicine, Nanjing, 210046, China.

出版信息

Neurotox Res. 2019 Nov;36(4):756-763. doi: 10.1007/s12640-019-00079-x. Epub 2019 Jun 26.

Abstract

Tourette syndrome (TS) is characterized by one of the chronic neuropsychiatric disorders in multiple children, and the pathogenesis of Tourette syndrome (TS) has not been previously elucidated.The aim of this study was designed to investigate the effects of rhynchophylline (RH) on Tourette syndrome (TS) in rats.TS model was established in rats and BV2 cells by the selective 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Behavior evaluations including stereotypy recording and autonomic activity test were performed. Inflammatory cytokine levels such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum, striatum, and cell supernatant were detected. The expression levels of BDNF/NF-κB pathway in striatum and BV2 cells were measured by Western blot. Dopamine (DA) and dopamine receptor D 2 (D2) in striatum were also measured.Data indicated that RH significantly decreased IL-6, IL-1β, and TNF-α in serum, striatum, and cell supernatant of TS model, with altered expression of P-NF-κBp65, P-IκBα, and BDNF in TS rats, and DOI-induced BV2 cells, as evidenced by Western blot analysis and immunohistochemistry analysis. RH also significantly reduced the levels of DA and D2 in striatum.Our results shown that the regulation of BDNF/NF-κB pathway might be involved in the effects of RH on TS model.

摘要

妥瑞氏综合征(TS)是一种多发于儿童的慢性神经精神障碍疾病,其发病机制尚未明确。本研究旨在探讨钩藤碱(RH)对大鼠妥瑞氏综合征(TS)的影响。通过选择性 5-羟色胺 2A/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 模型和 BV2 细胞模型。进行刻板行为记录和自主活动测试等行为评估。检测血清、纹状体和细胞上清液中白细胞介素 1β(IL-1β)、白细胞介素 6(IL-6)和肿瘤坏死因子-α(TNF-α)等炎症细胞因子水平。通过 Western blot 测量纹状体和 BV2 细胞中 BDNF/NF-κB 通路的表达水平。还测量了纹状体中的多巴胺(DA)和多巴胺受体 D2(D2)。数据表明,RH 可显著降低 TS 模型血清、纹状体和细胞上清液中的 IL-6、IL-1β和 TNF-α,改变 TS 大鼠和 DOI 诱导的 BV2 细胞中 P-NF-κBp65、P-IκBα和 BDNF 的表达,Western blot 分析和免疫组化分析证实了这一点。RH 还显著降低了纹状体中的 DA 和 D2 水平。我们的结果表明,BDNF/NF-κB 通路的调节可能参与了 RH 对 TS 模型的作用。

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