中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (1): 194-199.doi: 10.4103/1673-5374.343892

• 原著:退行性病与再生 • 上一篇    下一篇

DL-3-正丁基苯酞抑制帕金森病铁死亡改善运动功能障碍

  

  • 出版日期:2023-01-15 发布日期:2022-06-17
  • 基金资助:
    国家自然科学基金项目(81873924,82171190);南通科技项目(MS22021010);江苏省高层次创新创业人才引进计划项目

DL-3-n-butylphthalide alleviates motor disturbance by suppressing ferroptosis in a rat model of Parkinson’s disease

Chun-Bo Hu1, 2, #, Hui Jiang2, #, Yin Yang1, Guo-Hua Wang2, Qiu-Hong Ji1, Zhong-Zheng Jia3, Li-Hua Shen1, *, Qian-Qian Luo2, *   

  1. 1Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China; 2Department of Physiology and Hypoxic Biomedicine, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China; 3Department of Medical Imaging, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
  • Online:2023-01-15 Published:2022-06-17
  • Contact: Li-Hua Shen, MD, PhD, lihuashennt@126.com; Qian-Qian Luo, PhD, qianqianluo@ntu.edu.cn.
  • Supported by:
    This work was funded by the National Natural Science Foundation of China, No. 81873924 (to QQL), No. 82171190 (to GHW); Nantong Science and Technology Project of China, No. MS22021010 (to LHS); and High-level Innovation and Entrepreneurship Talents Introduction Program of Jiangsu Province of China (to QQL).

摘要:

既往研究已证实从中国芹菜中分离纯化出的化合物DL-3-正丁基苯酞可通过多种机制对脑缺血发挥保护作用,已被批准用于急性缺血性脑卒中的临床治疗。最近,有研究显示DL-3-正丁基苯酞对帕金森病也有治疗潜力,但其具体机制不明。实验以连续28d腹腔注射鱼藤酮建立帕金森病大鼠模型,在14-28d时灌胃DL-3-正丁基苯酞进行治疗。结果发现DL-3-正丁基苯酞能明显减轻鱼藤酮诱导的帕金森病大鼠运动障碍,抑制黑质中多巴胺能神经元丢失以及α-突触核蛋白的聚集,同时减少黑质内铁沉积以及血浆中的铁含量,且这一功能是通过改变转铁蛋白、储铁蛋白轻链、铁转运蛋白等铁代谢相关蛋白的表达来实现的。DL-3-正丁基苯酞还能抑制帕金森病大鼠黑质中的氧化应激并保护线粒体。表明DL-3-正丁基苯酞可通过抑制帕金森病大鼠黑质区铁沉积、氧化应激及多巴胺能神经元铁死亡,减轻其运动障碍。

https://orcid.org/0000-0001-8302-3117 (Qian-Qian Luo)

关键词:

帕金森病, 铁, 氧化应激, DL-3-正丁基苯酞, 鱼藤酮, 铁死亡, 转铁蛋白受体, 铁转运蛋白 1, 铁蛋白轻链, xCT, 谷胱甘肽过氧化物酶4

Abstract: DL-3-n-butylphthalide (NBP)—a compound isolated from Apium graveolens seeds—is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke. NBP has shown recent potential as a treatment for Parkinson’s disease. However, the underlying mechanism of action of NBP remains poorly understood. In this study, we established a rat model of Parkinson’s disease by intraperitoneal injection of rotenone for 28 successive days, followed by intragastric injection of NBP for 14–28 days. We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson’s disease, inhibited loss of dopaminergic neurons and aggregation of α-synuclein, and reduced iron deposition in the substantia nigra and iron content in serum. These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor, ferritin light chain, and transferrin 1. NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson’s disease. Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition, oxidative stress, and ferroptosis in the substantia nigra.

Key words: cystine/glutamate antiporter solute carrier family 7 member 11, DL-3-n-butylphthalide, ferritin light chain, ferroportin 1, ferroptosis, glutathione peroxidase 4, oxidative stress, iron, rotenone, transferrin receptor