Background

Tourette syndrome (TS) is a chronic neuropsychiatric disorder, also known as multiple tic syndrome. TS is associated with the serotonin (5-HT) system, of which 5-HT2A is a subtype. Xiaoyao San (XYS) comes from “Prescriptions of the Bureau of Taiping People’s Welfare”. It has the effect of harmonizing liver and spleen, relieving depression, nourishing blood, and invigorating spleen. However, the therapeutic mechanism of XYS for TS has not been evaluated. This study aimed to investigate the therapeutic effect of XYS on the TS mouse model and its possible mechanism.

Methods

A mouse model of TS induced by DOI (selective 5-HT (2A/2C) receptor agonist, 10 ml/kg) was established. The mice were randomly divided into normal control group, DOI group, DOI + Tiapride Hydrochloride (Tia at 25 mg /kg) group, DOI + XYS low-dose (1.44 g/kg/d), medium-dose (2.88 g/kg/d) and high-dose (5.76 g/kg/d) groups, and the mice were given the corresponding drug intragastric administration for four consecutive weeks, and the stereotypic behavior was recorded weekly. The morphological characteristics of the cells were observed by hematoxylin–eosin staining. The content of 5-HT was determined by enzyme-linked immunosorbent assay. Western blot and quantitative polymerase chain reaction were used to detect 5-HT2A.

Results

XYS could significantly improve the stereotypic behavior of TS mice, and the improvement effect increased with the increase of dose, the improvement effect of XYS high dose was similar to that of Tia. After Tia or XYS high-dose treatment, the prefrontal cortex cells and neuronal structure of TS mice gradually normal, cells arranged neatly. The prefrontal cortex cells recovered generally after XYS low-dose and medium-dose treatments. 5-HT in the serum of mice in all treatment groups was higher than that in the DOI group, and 5-HT in serum of XYS high-dose group and Tia group was the highest. 5-HT2A receptor protein and mRNA in the prefrontal cortex of mice in all treatment groups showed a downward trend, and the decrease degree was the largest in the XYS high-dose group and Tia group.

Conclusion

XYS has an improvement effect on TS in mice, and its mechanism is related to reducing 5-HT2A receptor expression, increasing 5-HT content, and enhancing 5-HT system activity. These results suggest that XYS is a therapeutic strategy for TS treatment.

中文翻译：

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逍遥散对抽动秽语综合征小鼠神经功能及5-HT2A mRNA表达影响的初步研究

背景

抽动秽语综合征（TS）是一种慢性神经精神疾病，也称为多发性抽动综合征。 TS 与血清素 (5-HT) 系统相关，5-HT2A 是其中的一个亚型。逍遥散（XYS）出自《太平人民福利局方》。具有调和肝脾、解郁、养血、健脾的功效。然而，XYS 治疗 TS 的治疗机制尚未得到评估。本研究旨在探讨XYS对TS小鼠模型的治疗作用及其可能的机制。

方法

建立DOI（选择性5-HT（2A/2C）受体激动剂，10ml/kg）诱导TS的小鼠模型。将小鼠随机分为正常对照组、DOI组、DOI+盐酸泰必利（Tia 25 mg/kg）组、DOI+XYS低剂量（1.44 g/kg/d）、中剂量（2.88 g/kg） /d）和高剂量（5.76 g/kg/d）组，连续4周给予相应药物灌胃，每周记录定型行为。苏木精-伊红染色观察细胞形态特征。采用酶联免疫吸附法测定5-HT含量。采用Western blot和定量聚合酶链反应检测5-HT2A。

结果

XYS能显着改善TS小鼠的刻板行为，且改善效果随剂量的增加而增强，XYS高剂量的改善效果与Tia相似。经过Tia或XYS大剂量治疗后，TS小鼠的前额皮质细胞和神经元结构逐渐正常，细胞排列整齐。 XYS低剂量和中剂量治疗后，前额皮质细胞普遍恢复。各治疗组小鼠血清中5-HT含量均高于DOI组，其中XYS高剂量组和Tia组血清中5-HT含量最高。各治疗组小鼠前额皮质5-HT2A受体蛋白和mRNA均呈下降趋势，其中XYS高剂量组和Tia组下降幅度最大。

结论

XYS对小鼠TS有改善作用，其机制与降低5-HT2A受体表达、增加5-HT含量、增强5-HT系统活性有关。这些结果表明 XYS 是 TS 治疗的一种治疗策略。