背景:乌草是一种常用的治疗TD的中药,其主要成分是鱿鱼挥发油。乌草挥发油能保护神经细胞,缓解学习记忆障碍。然而,VOA的抗药机制尚不清楚。
目的:我们旨在探讨刺梨挥发油(VOA)对抽动障碍(TD)大鼠纹状体多巴胺能和谷氨酸能系统以及突触可塑性的影响,以及其抗TD的药物机制。
方法:本研究涉及48只(3周龄)SD大鼠,随机分为两个主要组:对照组(8)和TD(40)。TD组大鼠腹腔注射3,3-亚氨基二丙腈(IDPN),构建TD大鼠模型。他们分为五个子组:模型,Tiapride,VOA-高,美国之音-媒介,和VOA低(N=8)。建模后,对VOA组大鼠灌胃给予VOA(1次/天,连续四周),空白对照组和模型组大鼠接受相同体积的生理盐水。使用刻板印象和运动行为评分反映了动物的行为变化。在干扰之后,纹状体神经元的模式和树突棘的密度进行了研究,使用H&E和高尔基染色,并使用透射电子显微镜(TEM)检查纹状体突触的超微结构。此外,使用Ca2+检测器测定Ca2+含量,ELISA法检测血清和纹状体中多巴胺(DA)和谷氨酸(GLU)含量。最后,DRD1,DRD2,AMPAR1,NMPAR1,DAT,VMAT2,CAMKⅡ,使用定量实时PCR(qRT-PCR)检测纹状体中的CREB表达,蛋白质印迹(WB)和免疫组织化学(IHC)方法。
结果:与空白对照组和模型组大鼠相比,VOA组大鼠的刻板行为评分较低。此外,VOA组的大鼠表现出缓解,神经元损伤和神经元树突和树突棘的数量增加,根据TEM图像显示,VOA组显示出清晰的突触结构,突触后致密物质和突触小泡的数量增加。VOA组还表现出降低的Ca2+含量,以及DRD1、DRD2、DAT的上调,AMPAR1和NMPAR1与VMAT-2、CAMKⅡ、和CREB在纹状体。
结论:总之,VOA可以通过调节多巴胺能和谷氨酸能系统来影响突触可塑性,从而缓解TD。
BACKGROUND: Acori graminei Rhizoma is a commonly used traditional Chinese medicine for treating TD, with its main component being calamus volatile oil. Volatile Oil from Acori graminei Rhizoma(VOA)can protect nerve cells and alleviate learning and memory disorders. However, the mechanism of anti-tic of VOA is still unclear.
OBJECTIVE: We aimed to explore the effects of Volatile Oil from Acori Tatarinowii Rhizoma (VOA) on striatal dopaminergic and glutamatergic systems and synaptic plasticity of rats with Tic Disorder (TD), as well as its pharmaceutical mechanism against TD.
METHODS: This study involved 48 (three-week-old) Sprague Dawley (SD) rats, which were randomly divided into two primary groups: Control (8) and TD (40). Rats in the TD group were injected intraperitoneally with 3,3-iminodipropionitrile (IDPN) to construct the TD rat model. They were divided into five subgroups: Model, Tiapride, VOA-high, VOA-medium, and VOA-low (N=8). After modeling, VOA was administrated to rats in the VOA groups through gavage (once/day for four consecutive weeks), while rats in the blank control and model groups received normal saline of the same volume. The animals\' behavioral changes were reflected using the stereotypic and motor behavior scores. After interferences, patterns of striatal neurons and the density of dendritic spines were investigated using H&E and Golgi staining, and the ultrastructure of striatal synapses was examined using Transmission Electron Microscopy (TEM). Furthermore, Ca2+ content was determined using the Ca2+ detector, and Dopamine (DA) and
Glutamate (GLU) contents in serum and striatum were detected through ELISA. Finally, DRD1, DRD2, AMPAR1, NMPAR1, DAT, VMAT2, CAMKⅡ, and CREB expression in the striatum was detected using Quantitative real-time PCR (qRT-PCR),Western Blotting (WB) and Immunohistochemical (IHC) methods.
RESULTS: Compared to rats in the blank control and model groups, rats in the VOA groups showed lower stereotypic behavior scores. Furthermore, rats in the VOA groups exhibited relieved, neuron damage and increased quantities of neuronal dendrites and dendritic spines Additionally, based on TEM images show that, the VOA groups showed a clear synaptic structure and increased amounts of postsynaptic dense substances and synaptic vesicles. The VOA groups also exhibited reduced Ca2+ contents, and upregulation of DRD1, DRD2, DAT, AMPAR1, and NMPAR1 and downregulation of VMAT-2, CAMKⅡ, and CREB in the striatum.
CONCLUSIONS: In summary, VOA could influence synaptic plasticity by tuning the dopaminergic and glutamatergic systems, thus relieving TD.