中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (3): 568-576.doi: 10.4103/1673-5374.350203

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

绿原酸能减轻新生小鼠缺氧缺血性脑损伤

  

  • 出版日期:2023-03-15 发布日期:2022-08-26
  • 基金资助:

    中国国家自然科学基金项目(81971425),浙江省自然科学基金项目(LY20H040002)

Chlorogenic acid alleviates hypoxic-ischemic brain injury in neonatal mice

Lu-Yao Li1, 2, #, Qi Wang2, #, Lu Deng3, Zhen Lin4, Jing-Jing Lin5, Xin-Ye Wang2, Tian-Yang Shen2, Yi-Hui Zheng2, Wei Lin2, Pei-Jun Li3, Xiao-Qin Fu2, *, Zhen-Lang Lin2, *   

  1. 1Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; 2Department of Neonatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; 3Department of Geriatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; 4Department of Orthopedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; 5Department of Neurology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
  • Online:2023-03-15 Published:2022-08-26
  • Contact: Zhen-Lang Lin, MD, PhD, linzhenlang@hotmail.com; Xiao-Qin Fu, PhD, fuxq@wzhealth.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81971425, and the Natural Science Foundation of Zhejiang Province, No. LY20H040002 (both to XQF).

摘要:

最近有研究认为,咖啡的主要提取物绿原酸可能对神经系统有一定的保护作用,但其对新生儿缺氧缺血性脑损伤是否有保护作用尚待研究。实验以改良Rice-Vannucci法构建了新生小鼠缺氧缺血性脑损伤模型,并腹腔注射绿原酸进行治疗。结果显示:(1)绿原酸有效地缩小了模型小鼠的脑梗死体积,减轻脑水肿,恢复脑组织结构,并促进损伤脑组织中轴突的生长。(2)进一步以氧糖剥夺原代皮质神经元模型进行观察,发现绿原酸预处理减轻原代神经元的氧糖剥夺损伤,并促进神经元的存活。(3)最后发现绿原酸能逆转缺氧缺血性脑损伤新生模型小鼠脑组织中铁死亡相关蛋白的表达,且谷胱甘肽过氧化物酶4及其上游谷氨酸/胱氨酸逆向转运蛋白相关因子 SLC7A11 和 SLC3A2 的表达也明显上调。(4)这些数据一定程度上说明绿原酸通过减少铁死亡减轻了新生小鼠缺氧缺血性脑损伤,为新生儿缺氧缺血性脑损伤的治疗提供了动物实验的客观数据和新的思路。

https://orcid.org/0000-0003-1637-7622 (Zhen-Lang Lin); 

https://orcid.org/0000-0001-6354- 8960 (Xiao-Qin Fu); 

https://orcid.org/0000-0001-9457-8329 (Lu-Yao Li).

关键词: 绿原酸, 新生儿缺氧缺血性脑损伤, 神经保护, Xc-, 谷胱甘肽过氧化物酶4, 铁死亡, 脂质过氧化, 神经元, 氧糖剥, 氧化应激

Abstract: Recent studies have shown that chlorogenic acid (CGA), which is present in coffee, has protective effects on the nervous system. However, its role in neonatal hypoxic-ischemic brain injury remains unclear. In this study, we established a newborn mouse model of hypoxic-ischemic brain injury using a modified Rice-Vannucci method and performed intraperitoneal injection of CGA. We found that CGA intervention effectively reduced the volume of cerebral infarct, alleviated cerebral edema, restored brain tissue structure after injury, and promoted axon growth in injured brain tissue. Moreover, CGA pretreatment alleviated oxygen-glucose deprivation damage of primary neurons and promoted neuron survival. In addition, changes in ferroptosis-related proteins caused by hypoxic-ischemic brain injury were partially reversed by CGA. Furthermore, CGA intervention upregulated the expression of the key ferroptosis factor glutathione peroxidase 4 and its upstream glutamate/cystine antiporter related factors SLC7A11 and SLC3A2. In summary, our findings reveal that CGA alleviates hypoxic-ischemic brain injury in neonatal mice by reducing ferroptosis, providing new ideas for the treatment of neonatal hypoxic-ischemic brain injury.

Key words: chlorogenic acid, ferroptosis, glutathione peroxidase 4, lipid peroxidation, neonatal hypoxic-ischemic brain injury, neurons, neuroprotection, oxidative stress, oxygen-glucose deprivation, system Xc–