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益气温阳散寒方对帕金森病小鼠的神经保护作用及机制

Neuroprotective effects and mechanisms of the YiQiWenYangSanHan formula on Parkinson's disease mice.

作者信息

Liu Jinling, Di Dong, Sun Suping, Sun Yan, Zhou Shihan, Liu Jing, Qin Zizhen, Yang Xinyu, Wang Xiao, Xu Zheng, Zhu Boran, Wu Haoxin

机构信息

Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.

Key Laboratory of Integrative Biomedicine for Brain Diseases, College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, China.

出版信息

IBRO Neurosci Rep. 2025 Apr 1;18:528-538. doi: 10.1016/j.ibneur.2025.03.014. eCollection 2025 Jun.

Abstract

BACKGROUND

Parkinson's disease (PD) is a complex neurodegenerative disease, which is often treated with obvious side effects such as dopamine replacement therapy. Our team has validated the unique advantages of the traditional Chinese medicine formula, YiQiWenYangSanHan formula (YQWYSHF), through in vitro experiments, confirming its therapeutic potential for PD. Nevertheless, further research and validation are required to fully understand its protective effects and underlying mechanisms against PD.

AIM OF THIS REVIEW

This study employed an in vivo model to investigate the effects of YQWYSHF on motor impairments, neuroinflammation, and mitochondrial dysfunction in C57BL/6 J mice caused by MPTP.

MATERIALS AND METHODS

Sixty C57BL/6 J mice were randomly divided into 5 groups, all groups except the control group were intraperitoneally administered MPTP for 7 days (30 mg/kg). After 4 weeks of drug intragastric treatment, we assessed the dyskinesia of mice treated with different doses of YQWYSHF by behavioral examination. Additionally, immunofluorescence was used to examine the expression of ionized calcium binding adaptor protein 1 (IBA1) and glial fibrillary acidic protein-positive (GFAP) cells. Western blotting was used to assess the expression level of tyrosine hydroxylase (TH), pyrin domain-containing 3 protein (NLRP3), apoptosis-associated speck-like proteins (ASC), cysteine-containing aspartate protease-1 (Caspase-1), interleukin-1β (IL-1β), α-synuclein (α-syn), poly (ADP-ribose) polymerase 1 (PARP1), and poly ADP ribose (PAR). Furthermore, transmission electron microscopy revealed mitochondrial impairment in the neuronal cells of the substantia nigra (SN).

RESULTS

YQWYSHF treatment alleviated dyskinesia in a mouse model of PD. Moreover, it increased the TH expression, and could reverse the increase of IBA1, GFAP, NLRP3, ASC, caspase-1,IL-1β, α-syn, PARP1 and PAR proteins induced by MPTP.

CONCLUSIONS

YQWYSHF protects dopaminergic neurons in PD by attenuating neuroinflammation and mitochondrial dysfunction. This study provides new evidence for the clinical application of traditional Chinese medicine in the treatment of PD.

摘要

背景

帕金森病(PD)是一种复杂的神经退行性疾病,常采用多巴胺替代疗法等有明显副作用的治疗方法。我们的团队已通过体外实验验证了中药方剂益气温阳散寒方(YQWYSHF)的独特优势,证实了其对帕金森病的治疗潜力。然而,需要进一步的研究和验证,以充分了解其对帕金森病的保护作用及潜在机制。

本综述的目的

本研究采用体内模型,研究益气温阳散寒方对由1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的C57BL/6 J小鼠运动障碍、神经炎症和线粒体功能障碍的影响。

材料与方法

将60只C57BL/6 J小鼠随机分为5组,除对照组外,其余各组均腹腔注射MPTP 7天(30 mg/kg)。经过4周的药物灌胃治疗后,我们通过行为学检查评估不同剂量益气温阳散寒方治疗小鼠的运动障碍。此外,采用免疫荧光法检测离子钙结合衔接分子1(IBA1)和胶质纤维酸性蛋白阳性(GFAP)细胞的表达。采用蛋白质免疫印迹法评估酪氨酸羟化酶(TH)、含pyrin结构域蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)、含半胱氨酸的天冬氨酸蛋白水解酶1(Caspase-1)、白细胞介素-1β(IL-1β)、α-突触核蛋白(α-syn)、聚(ADP-核糖)聚合酶1(PARP1)和聚ADP核糖(PAR)的表达水平。此外,透射电子显微镜显示黑质(SN)神经元细胞中的线粒体损伤。

结果

益气温阳散寒方治疗减轻了帕金森病小鼠模型的运动障碍。此外,它增加了TH的表达,并能逆转由MPTP诱导的IBA1、GFAP、NLRP3、ASC、Caspase-1、IL-1β、α-syn、PARP1和PAR蛋白的增加。

结论

益气温阳散寒方通过减轻神经炎症和线粒体功能障碍来保护帕金森病中的多巴胺能神经元。本研究为中药在帕金森病治疗中的临床应用提供了新的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c695/11999681/07112e2fdd04/ga1.jpg

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