The functional role of hemojuvelin in acute ischemic stroke

Guang-Huar Young, Sung-Chun Tang, Vincent Wu, Kuo-Chuan Wang, Jing-Yi Nong, Po-Yuan Huang, Chaur-Jong Hu, H. Chiou, J. Jeng, C. Hsu
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引用次数: 12

Abstract

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; P = 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.
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血少年素在急性缺血性脑卒中中的功能作用
我们的研究旨在确定血少年素(HJV)在急性缺血性脑卒中(AIS)中的作用。我们对10名AIS和2名非卒中尸检受试者的脑组织进行了HJV表达的免疫组织化学检测。112例AIS患者脑卒中后48 h内血浆HJV测定。结果显示,与非卒中受试者相比,AIS患者脑组织中HJV表达显著增加。在调整临床变量后,脑卒中后48小时内血浆HJV水平是脑卒中后3个月功能预后不良的独立预测因子(OR:1.78, 95% CI: 1.03-3.07;p = 0.038)。在基础部分,Western blotting显示HJV在大脑中动脉闭塞(MCAO)后3 h表达明显,在72 h表达明显增加。在体外培养的皮质神经元中,氧葡萄糖剥夺(OGD) 24 h后HJV蛋白表达显著升高,小干扰rna (siHJV)转染的OGD神经元的凋亡率较低。重要的是,mcao 72 h后,与野生型小鼠相比,HJV敲除小鼠的梗死灶明显缩小,cleaved caspase-3蛋白的表达明显减少。综上所述,HJV参与脑卒中后神经元损伤的机制,血浆HJV水平可作为AIS患者潜在的早期预后指标。
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