宁动颗粒调节抽动-秽语综合征模型大鼠皮质-纹状体-丘脑环路多巴胺代谢机制研究

Tourette syndrome (TS) is a commonly neurobehavioral and neuropsychiatric disorder in children, and recent studies provide evidence implicating metabolic abnormalities of dopamine (DA) in cortico-striatal-thalamo-cortical (CSTC) circuits for its pathophysiology. Good efficacy has been shown on the treatment for TS according to syndrome differentiation in Traditional Chinese Medicine (TCM). Ningdong granule (NDG) has also been proved effective on TS for several years in our previous research, however, its mechanism still remains obscure. To evaluate the possible mechanism of NDG on metabolism of DA in TS model rats. Based on the previous studies, we have built TS model rats by microinfusing TS sera, and we have also shown that NDG can regulate metabolism of DA. However, its mechanism still remains obscure. To evaluate the possible mechanism of NDG on dopaminergic regulation of metabolism. In our study, we hope to find whether there are abnormalities for its related enzymologies, its metabolic product HVA and DOPAC, its receptors and its transporters of DA systems in CSTC.

抽动-秽语综合征(TS)是儿科神经及精神行为性疑难病，其病理生理机制与皮质-纹状体-丘脑相关环路(CSTC)内多巴胺(DA)代谢异常密切相关，中医药辨证论治治疗TS具有一定优势。临床研究已证实宁动颗粒对治疗心肝亏虚型抽动-秽语综合征(TS)有显著疗效，且我们的前期研究证实宁动颗粒具有调节CSTC内神经递质代谢作用，但其具体调节机制有待进一步阐明。基于前期研究，本课题设计拟采用富含抗神经抗体的心肝亏虚型TS患者血清诱导该证型的大鼠TS模型，采用分子生物学技术分析宁动颗粒对其血清中酪氨酸羟化酶及单胺氧化酶活性的影响，对纹状体匀浆DA及血清中DA代谢产物高香草酸(HVA) 和二羟基苯乙酸(DOPAC)浓度影响，及对纹状体内多DA D2受体(DAR2)和DA转运蛋白(DAT)表达的影响，以阐明宁动颗粒调节TS模型大鼠DA代谢作用机制。

抽动-秽语综合征(TS)是儿科神经及精神行为性疑难病，其病理生理机制与皮质-纹状体-丘脑相关环路(CSTC)内多巴胺(DA)代谢异常密切相关，中医药辨证论治治疗TS 具有一定优势。本研究使用TS患儿血清，微泵注射腹侧纹状体大鼠，成功诱导出类似于TS刻板行为症状。通过动物模型，证实宁动颗粒具有调节CSTC 内神经递质代谢作用：宁动颗粒更能改善心肝亏虚性TS患儿刻板行为，其机制可能与提高MAO、TH含量，增加TS模型大鼠纹状体DAT表达，增加DA代谢产物代谢产物高香草酸(HVA) 和二羟基苯乙酸(DOPAC)含量，而促进DA代谢作用。与此同时，研究还额外发现，与硫必利对照时，宁动颗粒能明显改善TS伴有睡眠障碍患儿的睡眠，并减轻硫必利的副反应。