Division of Scientific Research, Energenesis Biomedical, Taipei.
Stroke Center and Department of Neurology, National Taiwan University Hospital, Taipei.
J Cereb Blood Flow Metab. 2020 Jun;40(6):1316-1327. doi: 10.1177/0271678X19861448. Epub 2019 Jul 15.
Our study aimed to establish the role of hemojuvelin (HJV) in acute ischemic stroke (AIS). We performed immunohistochemistry for HJV expression in human brain tissues from 10 AIS and 2 non-stroke autopsy subjects. Plasma HJV was measured in 112 AIS patients within 48 h after stroke. The results showed significantly increased HJV expression in brain tissues from AIS patients compare to non-stroke subjects. After adjusting for clinical variables, plasma levels of HJV within 48 h after stroke were an independent predictor of poor functional outcome three months post-stroke (OR:1.78, 95% CI: 1.03-3.07; = 0.038). In basic part, Western blotting showed that HJV expression in mice brains was apparent at 3 h after middle cerebral artery occlusion (MCAO), and increased significantly at 72 h. In cultured cortical neurons, expression of HJV protein increased remarkably 24 h after oxygen glucose deprivation (OGD), and small interfering RNAs (siHJV) transfected OGD neurons had a lower apoptotic rate. Importantly, 72 h post-MCAO, HJV knockout mice had significantly smaller infarcts and less expression of cleaved caspase-3 protein compared with wild-type mice. In summary, HJV participates in the mechanisms of post-stroke neuronal injury, and that plasma HJV levels can be a potential early outcome indicator for AIS patients.
我们的研究旨在确定高铁血红素蛋白(HJV)在急性缺血性脑卒中(AIS)中的作用。我们对 10 名 AIS 患者和 2 名非中风尸检患者的人脑组织进行了 HJV 表达的免疫组织化学染色。在中风后 48 小时内,我们测量了 112 名 AIS 患者的血浆 HJV。结果显示,与非中风患者相比,AIS 患者脑组织中的 HJV 表达明显增加。在调整临床变量后,中风后 48 小时内的血浆 HJV 水平是中风后三个月不良功能结局的独立预测因子(OR:1.78,95%CI:1.03-3.07; = 0.038)。在基础部分,Western blot 显示,在大脑中动脉闭塞(MCAO)后 3 小时,小鼠大脑中的 HJV 表达明显,72 小时后显著增加。在培养的皮质神经元中,氧葡萄糖剥夺(OGD)后 24 小时 HJV 蛋白表达显著增加,转染 siHJV 的 OGD 神经元的凋亡率较低。重要的是,MCAO 后 72 小时,与野生型小鼠相比,HJV 敲除小鼠的梗死灶明显较小,且 cleaved caspase-3 蛋白的表达水平较低。总之,HJV 参与了卒中后神经元损伤的机制,而血浆 HJV 水平可能是 AIS 患者的潜在早期预后指标。