中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (8): 1795-1801.doi: 10.4103/1673-5374.332157

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

氧化型低密度脂蛋白受体1:脑出血治疗新靶点预测

  

  • 出版日期:2022-08-15 发布日期:2022-01-22
  • 基金资助:
    国家自然科学基金项目(81971125)

Oxidized low-density lipoprotein receptor 1: a novel potential therapeutic target for intracerebral hemorrhage

Hui-Yuan Zhang, Xi Lu, Yue-Han Hao, Ling Tang, Zhi-Yi He*   

  1. Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Online:2022-08-15 Published:2022-01-22
  • Contact: Zhi-Yi He, PhD, hezhiyi0301@sina.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81971125 (to ZYH).

摘要:

既往研究已发现,氧化型低密度脂蛋白受体1可在神经细胞中表达上调,并参与高血压引起的神经凋亡进程,且氧化型低密度脂蛋白受体1耗竭还可保护大脑免受高血压性脑卒中引起的脑损伤,因此其可能参与脑出血的进程。实验右侧基底神经节注射50 pmol/μL氧化型低密度脂蛋白受体1小干扰RNA以敲低OLR1,24h后注射VII型胶原酶构建脑出血模型。结果发现,氧化型低密度脂蛋白受体1敲低可减轻脑出血大鼠神经行为缺陷、脑水肿和神经元丢失,并减轻脑出血后脑组织中炎症反应和氧化应激。进一步探索其潜在机制,研究结果显示氧化型低密度脂蛋白受体1 沉默可抑制脑出血诱导的神经元铁死亡以及p38信号通路。由此得出,氧化型低密度脂蛋白受体1 沉默可通过抑制铁死亡对脑出血后继发性脑损伤的脑保护作用,这一过程是由p38信号通路介导的。提示氧化型低密度脂蛋白受体1有可能成为脑出血治疗的新靶点。

https://orcid.org/0000-0002-0995-0294 (Zhi-Yi He)

关键词: 氧化型低密度脂蛋白受体1, 脑出血, 铁死亡, p38信号通路, 炎症, 神经行为, 氧化应激, 继发性脑损伤, 神经保护, 治疗靶点

Abstract: Oxidized low-density lipoprotein receptor 1 (OLR1) is upregulated in neurons and participates in hypertension-induced neuronal apoptosis. OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive-induced stroke. Therefore, OLR1 is likely involved in the progress of intracerebral hemorrhage. In this study, we examined the potential role of OLR1 in intracerebral hemorrhage using a rat model. OLR1 small interfering RNA (10 μL; 50 pmol/μL) was injected into the right basal ganglia to knock down OLR1. Twenty-four hours later, 0.5 U collagenase type VII was injected to induce intracerebral hemorrhage. We found that knockdown of OLR1 attenuated neurological behavior impairment in rats with intracerebral hemorrhage and reduced hematoma, neuron loss, inflammatory reaction, and oxidative stress in rat brain tissue. We also found that silencing of OLR1 suppressed ferroptosis induced by intracerebral hemorrhage and the p38 signaling pathway. Therefore, silencing OLR1 exhibits protective effects against secondary injury of intracerebral hemorrhage. These findings suggest that OLR1 may be a novel potential therapeutic target for intracerebral hemorrhage.

Key words: ferroptosis, inflammation, intracerebral hemorrhage, neurological behavior, neuroprotection, novel therapeutic target, oxidative stress, oxidized low-density lipoprotein receptor 1, p38 signaling pathway, secondary brain injury