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安神定志灵通过对自发性高血压大鼠的抗炎作用减轻注意力缺陷多动障碍症状。

An Shen Ding Zhi Ling Alleviates Symptoms of Attention Deficit Hyperactivity Disorder via Anti-Inflammatory Effects in Spontaneous Hypertensive Rats.

作者信息

Song Yuchen, Yuan Haixia, Chen Tianyi, Lu Manqi, Lei Shuang, Han Xinmin

机构信息

Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Front Pharmacol. 2021 Jan 18;11:617581. doi: 10.3389/fphar.2020.617581. eCollection 2020.

Abstract

Attention deficit hyperactivity disorder (ADHD) is a childhood-onset chronic neurobehavioral disorder, with multiple genetic and environmental risk factors. Chronic inflammation may be critical for the progression of ADHD. An Shen Ding Zhi Ling (ASDZL) decoction, a traditional Chinese medicine prescription, is clinically used in ADHD treatment. In this study, we investigated the effects and underlying anti-inflammatory mechanisms of ASDZL in young spontaneously hypertensive rats (SHRs), a widely used model of ADHD. SHRs were divided into the SHR model group (vehicle), atomoxetine group (4.56 mg/kg/day) and ASDZL group (21.25 g/kg/day), and orally administered for four weeks. Wistar Kyoto rats were used as controls (vehicle). We found that ASDZL significantly controlled hyperactivity and impulsivity, and improved spatial memory of SHRs in the open field test and Morris water maze test. ASDZL reduced the pro-inflammatory factors interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 and increased anti-inflammatory factor IL-10 in SHRs, and decreased the activation of microglia, astrocytes and mast cells in the prefrontal cortex (PFC) and hippocampus. Furthermore, the results indicated that ASDZL inhibited the neuroinflammatory response by protecting the integrity of the blood-brain barrier and suppressing the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways of SHRs. In conclusion, these findings revealed that ASDZL attenuated ADHD symptoms in SHRs by reducing neuroinflammation.

摘要

注意缺陷多动障碍(ADHD)是一种起病于儿童期的慢性神经行为障碍,存在多种遗传和环境风险因素。慢性炎症可能对ADHD的进展至关重要。安神定志灵(ASDZL)汤是一种中药方剂,临床上用于治疗ADHD。在本研究中,我们研究了ASDZL对年轻自发性高血压大鼠(SHRs)的作用及其潜在的抗炎机制,SHRs是一种广泛应用的ADHD模型。将SHRs分为SHR模型组(溶剂)、托莫西汀组(4.56毫克/千克/天)和ASDZL组(21.25克/千克/天),并口服给药四周。以Wistar Kyoto大鼠作为对照(溶剂)。我们发现,在旷场试验和莫里斯水迷宫试验中,ASDZL显著控制了SHRs的多动和冲动行为,并改善了其空间记忆。ASDZL降低了SHRs中促炎因子白细胞介素(IL)-1β、IL-4、IL-6、肿瘤坏死因子(TNF)-α和单核细胞趋化蛋白(MCP)-1的水平,增加了抗炎因子IL-10的水平,并减少了前额叶皮质(PFC)和海马中微胶质细胞、星形胶质细胞和肥大细胞的活化。此外,结果表明,ASDZL通过保护血脑屏障的完整性并抑制SHRs的丝裂原活化蛋白激酶(MAPK)和核因子(NF)-κB信号通路来抑制神经炎症反应。总之,这些发现揭示了ASDZL通过减轻神经炎症来减轻SHRs的ADHD症状。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/7847841/d94b7ab5ce63/fphar-11-617581-g001.jpg

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