Deng Shuixiang, Liu Shengpeng, Jin Peng, Feng Shengjie, Tian Mi, Wei Pengju, Zhu Hongda, Tan Jiaying, Zhao Feng, Gong Ye
Department of Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China.
Department of Pediatrics, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China.
Oxid Med Cell Longev. 2021 Feb 24;2021:8891373. doi: 10.1155/2021/8891373. eCollection 2021.
Albumin has been regarded as a potent antioxidant with free radical scavenging activities. Oxidative stress and neuronal apoptosis are responsible for its highly damaging effects on brain injury after intracerebral hemorrhage (ICH). Here, the present study investigated the neuroprotective effect of albumin against early brain injury after ICH and the potential underlying mechanisms.
Adult male Sprague-Dawley rats were subjected to intrastriatal injection of autologous blood to induce ICH. Human serum albumin was given by intravenous injection 1 h after ICH. U0126, an inhibitor of extracellular signal-regulated kinase (ERK1/2), and ML385, an inhibitor of nuclear factor-E2-related factor 2 (Nrf2), were intraperitoneally administered 1 h before ICH induction. Short- and long-term neurobehavioral tests, western blotting, immunofluorescence staining, oxidative stress evaluations, and apoptosis measurements were performed.
Endogenous expression of albumin (peaked at 5 days) and heme oxygenase 1 (HO-1, peaked at 24 h) was increased after ICH compared with the sham group. Albumin and HO-1 were colocalized with neurons. Compared with vehicle, albumin treatment significantly improved short- and long-term neurobehavioral deficits and reduced oxidative stress and neuronal death at 72 h after ICH. Moreover, albumin treatment significantly promoted the phosphorylation of ERK1/2; increased the expression of Nrf2, HO-1, and Bcl-2; and downregulated the expression of Romo1 and Bax. U0126 and ML385 abolished the treatment effects of albumin on behavior and protein levels after ICH.
Albumin attenuated oxidative stress-related neuronal death may in part via the ERK/Nrf2/HO-1 signaling pathway after ICH in rats. Our study suggests that albumin may be a novel therapeutic method to ameliorate brain injury after ICH.
白蛋白被认为是一种具有自由基清除活性的强效抗氧化剂。氧化应激和神经元凋亡是脑出血（ICH）后脑损伤的高度破坏性影响的原因。在此，本研究探讨了白蛋白对ICH后脑早期损伤的神经保护作用及其潜在机制。
成年雄性Sprague-Dawley大鼠接受纹状体内自体血注射以诱导ICH。ICH后1小时静脉注射人血清白蛋白。在诱导ICH前1小时腹腔注射细胞外信号调节激酶（ERK1/2）抑制剂U0126和核因子E2相关因子2（Nrf2）抑制剂ML385。进行短期和长期神经行为测试、蛋白质印迹、免疫荧光染色、氧化应激评估和凋亡测量。
与假手术组相比，ICH后白蛋白（在第5天达到峰值）和血红素加氧酶1（HO-1，在24小时达到峰值）的内源性表达增加。白蛋白和HO-1与神经元共定位。与载体相比，白蛋白治疗显著改善了ICH后72小时的短期和长期神经行为缺陷，并降低了氧化应激和神经元死亡。此外，白蛋白治疗显著促进了ERK1/2的磷酸化；增加了Nrf2、HO-1和Bcl-2的表达；并下调了Romo1和Bax的表达。U0126和ML385消除了白蛋白对ICH后行为和蛋白质水平的治疗作用。
白蛋白减轻氧化应激相关的神经元死亡可能部分通过大鼠ICH后的ERK/Nrf2/HO-1信号通路。我们的研究表明，白蛋白可能是改善ICH后脑损伤的一种新的治疗方法。
