Department of Neurology, 904th Hospital of Joint Logistic Support Force of PLA, Wuxi Clinical College of Anhui Medical University, Wuxi, Jiangsu 214044, P.R. China.
Department of Nursing, 904th Hospital of Joint Logistic Support Force of PLA, Wuxi Clinical College of Anhui Medical University, Wuxi, Jiangsu 214044, P.R. China.
Mol Med Rep. 2021 Nov;24(5). doi: 10.3892/mmr.2021.12464. Epub 2021 Sep 24.
Spontaneous intracerebral hemorrhage (ICH) is a subtype of stroke associated with high mortality and morbidity due to the lack of effective therapy. Obstructive sleep apnea (OSA) has been reported to aggravate early brain injury (EBI) and worsen the overall outcome of patients with ICH. However, the precise role of OSA‑mediated neuroinflammation and apoptosis following ICH has not been confirmed. The present study aimed to investigate the neuronal damage induced by OSA and the potential molecular mechanisms by which ICH‑induced EBI regulates neural apoptosis in a C57BL/6 mouse ICH model. Mortality, neurological score, brain water content and neuronal death were evaluated by Evans blue extravasation, TUNEL staining, ELISA, analysis of reactive oxygen species/lipid peroxidation and western blotting. The results showed that OSA induction decreased survival rate, neurological score and neuron survival and upregulated the protein expression levels of Caspase‑3, Bax, cytokines IL‑1β, IL‑6 and TNF‑α and NF‑κB, which indicated that OSA‑mediated induction of apoptosis and neuroinflammation aggravated neuronal death following ICH. The molecular mechanism was partly dependent on the activating transcription factor/CHOP pathway. Taken together, the results demonstrated that OSA worsens neurological outcomes in mice and increases neuronal death by enhancing neural apoptosis and neuroinflammation.
自发性脑出血 (ICH) 是一种与高死亡率和发病率相关的中风类型，其原因在于缺乏有效的治疗方法。有研究报道阻塞性睡眠呼吸暂停 (OSA) 会加重早期脑损伤 (EBI)，并使 ICH 患者的整体预后恶化。然而，OSA 介导的神经炎症和细胞凋亡在 ICH 后的确切作用尚未得到证实。本研究旨在通过建立 C57BL/6 小鼠 ICH 模型，探讨 OSA 引起的神经元损伤以及 ICH 诱导的 EBI 调节神经细胞凋亡的潜在分子机制。通过 Evans 蓝渗出、TUNEL 染色、ELISA、活性氧/脂质过氧化分析和 Western blot 分析评估死亡率、神经评分、脑水含量和神经元死亡。结果表明，OSA 的诱导降低了存活率、神经评分和神经元存活，并上调了 Caspase-3、Bax、细胞因子 IL-1β、IL-6 和 TNF-α 以及 NF-κB 的蛋白表达水平，这表明 OSA 介导的细胞凋亡和神经炎症的诱导加重了 ICH 后的神经元死亡。其分子机制部分依赖于激活转录因子/CHOP 通路。综上所述，研究结果表明，OSA 通过增强神经细胞凋亡和神经炎症，使小鼠的神经功能结局恶化，并增加神经元死亡。
