Zhang Hui-Yuan, Lu Xi, Hao Yue-Han, Tang Ling, He Zhi-Yi
Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China.
Neural Regen Res. 2022 Aug;17(8):1795-1801. doi: 10.4103/1673-5374.332157.
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.
氧化型低密度脂蛋白受体1（OLR1）在神经元中上调，并参与高血压诱导的神经元凋亡。OLR1缺失对高血压性中风所致脑损伤具有保护作用。因此，OLR1可能参与脑出血的进展。在本研究中，我们使用大鼠模型研究了OLR1在脑出血中的潜在作用。将OLR1小干扰RNA（10 μL；50 pmol/μL）注射到右侧基底神经节以敲低OLR1。24小时后，注射0.5 U VII型胶原酶以诱导脑出血。我们发现敲低OLR1可减轻脑出血大鼠的神经行为损伤，并减少大鼠脑组织中的血肿、神经元丢失、炎症反应和氧化应激。我们还发现沉默OLR1可抑制脑出血诱导的铁死亡和p38信号通路。因此，沉默OLR可对脑出血继发性损伤发挥保护作用。这些发现表明，OLR1可能是脑出血的一个新的潜在治疗靶点。
