Key Laboratory of Etiologic Epidemiology of Ministry of Health (23618104), Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang Province, China.
Oxid Med Cell Longev. 2013;2013:474203. doi: 10.1155/2013/474203. Epub 2013 Aug 26.
Oxidative stress and selenoprotein deficiency are thought to be associated with the pathogenesis of Keshan disease (KD). However, to our knowledge, the level of oxidative stress and expression of selenoproteins have not been investigated in the myocardium of patients with KD. In this study, 8-hydroxy-2-deoxy guanosine (8-OH-dG), a marker of oxidative stress, was used to assess the level of oxidative stress, and thioredoxin reductase 1 (TrxR1) and glutathione peroxidase 1 (GPx1) were assessed to reflect the level of selenoproteins. Myocardial samples from 8 patients with KD and 9 non-KD patients (controls) were immunohistochemically stained for 8-OH-dG, TrxR1, and GPx1. The staining intensities were subsequently quantified using Olympus Image-Pro Plus 6.0 software. The data showed that the positive rate of 8-OH-dG expression in myocardial nuclei was higher in the KD group (68.6%) than that in the control group (2.4%). In addition, a positive correlation between the positive rate of 8-OH-dG and the degree of myocardial damage was observed in the KD group. The distribution of TrxR1 and GPx-1 was not associated with the distribution of myocardial damage. The expression of these two selenoproteins was higher in the control group than that in the KD group. Our study represents the first report on the expression profiles of oxidative stress and selenoproteins in the myocardium of patients with KD. The level of oxidative stress significantly increased and was positively correlated with the degree of myocardial damage in patients with KD. The selenoproteins, TrxR1 and GPx1, may have a role in the pathogenesis of KD.
氧化应激和硒蛋白缺乏被认为与克山病(KD)的发病机制有关。然而,据我们所知,KD 患者心肌中氧化应激水平和硒蛋白的表达尚未得到研究。在本研究中,使用 8-羟基-2-脱氧鸟苷(8-OH-dG)作为氧化应激的标志物来评估氧化应激水平,并用硫氧还蛋白还原酶 1(TrxR1)和谷胱甘肽过氧化物酶 1(GPx1)来反映硒蛋白的水平。对 8 例 KD 患者和 9 例非 KD 患者(对照组)的心肌样本进行了 8-OH-dG、TrxR1 和 GPx1 的免疫组织化学染色。随后使用 Olympus Image-Pro Plus 6.0 软件对染色强度进行定量。数据显示,KD 组心肌核中 8-OH-dG 表达的阳性率(68.6%)高于对照组(2.4%)。此外,在 KD 组中观察到 8-OH-dG 阳性率与心肌损伤程度之间存在正相关。TrxR1 和 GPx-1 的分布与心肌损伤的分布无关。这两种硒蛋白在对照组中的表达高于 KD 组。本研究代表了 KD 患者心肌中氧化应激和硒蛋白表达谱的首次报告。氧化应激水平显著升高,并与 KD 患者的心肌损伤程度呈正相关。硒蛋白 TrxR1 和 GPx1 可能在 KD 的发病机制中起作用。