天麻素可改善多发性抽动症模型大鼠的头部抽动行为

目的 探讨天麻素对多发性抽动症（TS）模型大鼠头部抽动行为的影响及相关机制。方法 采用1-（2，5- 二甲氧基-4-碘苯基）-2-氨基丙烷（DOI）诱导法制备TS大鼠模型，将40只Wistar大鼠随机均分为4组：正常组（生理 盐水灌胃）、TS模型组（从造模首日起，注射DOI后2 h以生理盐水灌胃）、TS+天麻素组（从造模首日起，注射DOI后2 h以 30 mg/kg天麻素灌胃）；TS+天麻素+CHIR-99021［糖原合酶激酶-3β（GSK-3β）抑制剂］组（从造模首日起，注射DOI后 2 h，先以2 mg/kg CHIR-99021腹腔注射，再以30 mg/kg天麻素灌胃），连续给药21 d。末次给药后，记录大鼠在30 min 内的头部抽动次数，采用试剂盒检测纹状体5-羟色胺（5-HT）、5-羟吲哚乙酸（5-HIAA）、多巴胺（DA）水平，免疫组化 法检测黑质中 DA 神经元数量，Western blot 法检测纹状体中 5-羟色胺转运蛋白（SERT）、5-羟色胺 2A 受体（5- HT2AR）、5-羟色胺2C受体（5-HT2CR）表达及GSK-3β磷酸化情况。结果 与正常组比较，TS模型组大鼠头部抽动 次数、DA 水平、DA 神经元数量、SERT 水平及 p-S9-GSK-3β、p-S9-GSK-3β/t-GSK-3β 水平增高，5-HT 水平降低 （P＜0.05）。与TS模型组比较，TS+天麻素组大鼠头部抽动次数、DA水平、DA神经元数量、SERT水平及p-S9-GSK- 3β、p-S9-GSK-3β/t-GSK-3β水平降低，5-HT水平升高（P＜0.05）。与TS+天麻素组比较，TS+天麻素+CHIR-99021 组大鼠头部抽动次数、DA水平、DA神经元数量、SERT水平及p-S9-GSK-3β、p-S9-GSK-3β/t-GSK-3β水平升高，5- HT水平降低（P＜0.05）。结论 天麻素可改善TS大鼠头部抽动行为，其作用机制可能是通过抑制GSK-3β的磷酸 化，调节SERT表达，影响5-HT水平，进而抑制纹状体中DA的释放。

Gastrodin can improve the head twitch behavior of rats with Tourette syndrome

Objective To investigate the effect and mechanism of gastrodin on head twitch behavior in rats with Tourette syndrome (TS). Methods 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) induction method was used to replicate TS rat model. Forty Wistar rats were randomly divided into four groups (n=10): the normal group (gastric administration of normal saline), the TS model group (from the first day of modeling, intragastric administration with normal saline at 2 h after DOI injection), the TS+ gastrodin group (from the first day of modeling, intragastric administration with 30 mg/kg gastrodin at 2 h after DOI injection), and the TS+gastrodin+CHIR-99021 group glycogen synthase kinase-3β (GSK- 3β) inhibitor] (from the first day of modeling, 2 h after DOI injection, intraperitoneal injection with 2 mg/kg CHIR-99021 firstly, and then intragastric administration with 30 mg/kg gastrodin), continuous administration for 21 d. After the last administration, the rat’s head twitching behavior within 30 min was counted. The levels of striatal 5-hydroxyindole (5-HT), 5-hydroxyindole acetic acid (5-HIAA), and dopamine (DA) were detected by kits. The number of DA neurons in the substantia nigra was detected by immunohistochemical method. The expression of 5-HT transporter (SERT), 5- hydroxyindole 2A receptor (5-HT2AR), 5-hydroxyindole 2C receptor (5-HT2CR) and GSK-3β phosphorylation in the striatum were detected by Western blot assay. Results Compared with the normal group, the number of head twitches, DA level, number of DA neurons, SERT level and p-S9-GSK-3β, p-S9-GSK-3β/t-GSK-3β level increased in the TS model group, and the 5-HT level decreased (P＜0.05). Compared with the TS model group, the number of head twitches, DA level, number of DA neurons, SERT level and p-S9-GSK-3β, p-S9-GSK-3β/t-GSK-3β level decreased in the TS+gastrodin group, and the 5-HT level increased (P＜0.05). Compared with the TS+gastrodin group, the number of head twitches, DA level, number of DA neurons, SERT level and p-S9-GSK-3β, p-S9-GSK-3β/t-GSK-3β level increased , and the 5-HT level decreased in the TS+gastrodin+CHIR-99021 group (P＜0.05). Conclusion Gastrodin can improve the head twitch behavior of TS rats, and its mechanism may be by inhibiting the phosphorylation of GSK-3β, regulating the expression of SERT, affecting the level of 5-HT, and then inhibiting the release of DA in striatum.