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周姗,谢静,姚冰,陈佳,刘思佳,梁旋.基于黑质-纹状体多巴胺通路研究多发性抽动症“肝风”发生发展机制及泻青丸干预作用[J].湖南中医药大学学报英文版,2022,42(5):762-766.[Click to copy
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| 基于黑质-纹状体多巴胺通路研究多发性抽动症“肝风”发生发展机制及泻青丸干预作用 |
| 周姗,谢静,姚冰,陈佳,刘思佳,梁旋 |
| (湖南中医药大学第一附属医院, 湖南 长沙 410007;湖南中医药大学, 湖南 长沙 410208) |
| 摘要: |
| 目的 探讨泻青丸对多发性抽动症（Tourette syndrome, TS）模型大鼠行为学及黑质-纹状体多巴胺（dopamine, DA）通路的干预作用及TS“肝风”可能的微观实质。方法 从50只大鼠中随机抽取40只，均采用亚氨基二丙腈造模。造模成功后，将模型大鼠随机分为模型组、硫必利组、泻青丸高剂量组、泻青丸低剂量组，未造模处理的大鼠作为空白组，每组10只。硫必利组予以盐酸硫必利片混悬液30 mg/kg灌胃，空白组、模型组予以蒸馏水灌胃。泻青丸低、高剂量组分别予以0.45、0.90 g/mL泻青丸煎剂灌胃。各组均连续灌胃14 d。于造模7 d和灌胃7、14 d，记录大鼠体质量、行为（包括刻板行为及运动行为）评分。灌胃14 d后，脱颈处死，断头取脑，采用ELISA法检测纹状体中DA、高香草酸（homovanillic acid, HVA）含量。结果 造模7 d和灌胃7、14 d，模型组运动和刻板行为评分均明显高于空白组（P<0.05）。灌胃14 d，泻青丸低、高剂量组运动和刻板行为评分均明显低于模型组（P<0.01），且泻青丸低、高剂量组运动和刻板行为评分均明显低于硫必利组（P<0.05）。造模7 d、灌胃14 d，模型组体质量均明显小于空白组（P<0.05）。灌胃14 d，泻青丸低、高剂量组体质量均明显大于模型组及硫必利组（P<0.05，P<0.01）。模型组DA、HVA含量均明显高于空白组（P<0.05，P<0.01）。硫必利组、泻青丸低剂量组、泻青丸高剂量组DA、HVA含量均明显低于模型组（P<0.01）。结论 泻青丸能够明显改善TS模型大鼠刻板行为及异常运动行为，调节大鼠黑质-纹状体DA通路中DA、HVA的代谢。DA的代谢紊乱可能是TS肝风失衡的内在微观实质。 |
| 关键词: 多发性抽动症 泻青丸 亚氨基二丙腈 单胺类神经递质 肝风 |
| DOI：10.3969/j.issn.1674-070X.2022.05.012 |
| Received:October 29, 2021 |
| 基金项目:湖南中医药大学中医学国内一流建设学科项目（4901-020002002）；湖南省卫健委课题（20200830）；湖南中医药大学研究生创新课题（2019CX76）。 |
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| Study on the occurrence and development mechanism of "liver wind" in multiple tic syndrome and the intervention effect of Xieqing Pill based on substantia-nigra striatum dopamine pathway |
| ZHOU Shan,XIE Jing,YAO Bing,CHEN Jia,LIU Sijia,LIANG Xuan |
| (The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To investigate the effect of Xieqing Pill on the behavior and substantia-nigra striatum dopamine (DA) pathway in Tourette syndrome (TS) model rats and the possible microsubstance of TS "liver wind". Methods 40 rats were randomly selected from 50 rats and were modeled with iminodipropyl nitrile. After modeling, the model rats were randomly divided into model group, tiapride group, Xieqing Pill high-dose group and Xieqing Pill low-dose group, the rats without modeling treatment were used as blank group, with 10 rats in each group. Tiapride group was given tiapride hydrochloride tablet suspension 30 mg/kg intragastric administration, and blank group and model group were given distilled water intragastric administration. Xieqing Pill high-dose group and Xieqing Pill low-dose group were given 0.45 and 0.90 g/mL, respectively. All groups were given continuous gavage for 14 days. Body weight and behavioral scores (including stereotyped behavior and motor behavior) of rats were recorded at 7 d of modeling, 7 d of intragastric administration and 14 d of intragastric administration. All groups were given continuous gavage for 14 days. Body weight and behavior (including stereotyped behavior and motor behavior) scores of rats were recorded at 7 d after modeling, 7 d and 14 d after intragastric administration. After 14 days of intragastric administration, the rats were killed by neck removal, and the brains were cut off. The content levels of DA and homovanillic acid (HVA) in striatum were determined by ELISA. Results The scores of motor and stereotyped behavior in model group were significantly higher than those in blank group at 7 d after modeling, 7 d and 14 d after intragastric administration (P<0.05). After 14 days of intragastric administration, the scores of motor and stereotyped behavior in Xieqing Pill low-dose group and Xieqing Pill high-dose group were significantly lower than those in model group (P<0.01), and the scores of motor and stereotyped behavior in Xieqing Pill low-dose group and Xieqing Pill high-dose group were significantly lower than those in tiapride group (P<0.05). The body weight of model group was significantly lower than that of blank group at 7 d after modeling and 14 d after intragastric administration (P<0.05). After 14 days of intragastric administration, the body weight of Xieqing Pill low-dose group and Xieqing Pill high-dose group was significantly higher than that of model group and tiapride group (P<0.05, P<0.01). DA and HVA content levels in model group were significantly higher than those in blank group (P<0.05, P<0.01). The content levels of DA and HVA in tiapride group, Xieqing Pill low-dose group and Xieqing Pill high-dose group were significantly lower than those in model group (P<0.01). Conclusion Xieqing Pill can improve the stereotyped behavior and abnormal motor behavior of TS model rats, regulate the metabolism of DA and HVA in substantia-nigra striatum DA pathway. The metabolic disorder of DA may be the internal micro essence of the imbalance of liver wind in TS. |
| Key words: multiple tic syndrome Xieqing Pill iminodipropyl nitrile monoamine neurotransmitters liver wind |
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