Rhynchophylline Attenuates Neurotoxicity in Tourette Syndrome Rats
Rhynchophylline Attenuates Neurotoxicity in Tourette Syndrome Rats
复制标题
钩藤碱减轻抽动秽语综合征大鼠的神经毒性
DOI：
10.1007/s12640-019-00059-1
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发表时间：
2019-11-01
影响因子：
3.7
通讯作者：
Huang Yaruo
中科院分区：
文献类型：
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作者：
Long Hongyan;Zhang Mengjiao;Huang Yaruo
抽动秽语综合征（TS）是一种慢性神经精神疾病，临床表现为不自主、反复的肌肉抽搐和声带抽搐。用于治疗TS的药物相对有限。本研究的目的是探讨柳叶碱（RH）在1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI）诱导的TS大鼠神经毒性中的作用及其机制。DOI诱导TS模型。将大鼠分为对照组、TS组、TS +噻必利组（25 mg/kg）和TS + RH组（20、40 mg/kg）。行为学测试于末次给药24 h后进行，包括点头实验和刻板印象实验。采用酶联免疫吸附试验（ELISA）检测纹状体和血清中白细胞介素-6 （IL-6）、IL-1β和肿瘤坏死因子-α (TNF-α)水平。Western blot检测纹状体中toll样受体(TLR)/核苷酸结合域（NOD）样受体蛋白3 (NLRP3)/核因子κB （NF-κB）信号蛋白的表达水平。免疫组化法检测TLR2和NF-κB p65亚基的表达。RH可显著改善doi诱导的TS大鼠行为改变，降低血清和纹状体炎症因子水平。RH可抑制TS大鼠纹状体中TLR/NLRP3/NF-κB信号蛋白的激活。在BV2细胞中，通过TLR/NLRP3/NF-κB介导的doi诱导的炎症在RH给药后被显著抑制。研究RH对TS的治疗作用，明确其在体外和体内通过TLR/NLRP3/NF-κB通路介导的作用机制。
Tourette syndrome (TS) is a chronic neuropsychiatric disorder with clinical manifestations of involuntary and repeated muscle twitching and vocal twitching. The drugs used to treat TS are relatively limited. The aim of this study was to investigate the effects of rhynchophylline (RH) and the underlying mechanism in 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)–induced neurotoxicity in a TS rat model. A TS model was induced with DOI. The rats were divided into control, TS, TS + tiapride (25 mg/kg), and TS + RH (20 and 40 mg/kg) groups. Behavioral tests were performed 24 h after the last administration by nodding and stereotype experiments. Interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) levels in striatum and serum were detected with an enzyme-linked immunosorbent assay (ELISA). Western blot analysis was used to detect the expression levels of Toll-like receptor (TLR)/nucleotide-binding domain (NOD)–like receptor protein 3 (NLRP3)/nuclear factor kappa B (NF-κB) signal proteins in the striatum. The expression of TLR2 and NF-κB p65 subunit was detected with immunohistochemical analysis. RH may significantly improve behavioral changes in rats with DOI-induced TS and reduce the levels of inflammatory factors in serum and striatum. RH inhibited the activation of TLR/NLRP3/NF-κB signaling proteins in the striatum of TS rats. In BV2 cells, DOI-induced inflammation mediated through TLR/NLRP3/NF-κB was significantly inhibited following RH administration. The therapeutic effect of RH in TS was studied and its mechanism of action mediated via the TLR/NLRP3/NF-κB pathway was clarified in vitro and in vivo.