Lipid peroxidation dysregulation in ischemic stroke: Plasma 4-HNE as a potential biomarker?
Lipid peroxidation dysregulation in ischemic stroke: Plasma 4-HNE as a potential biomarker?
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DOI：
10.1016/j.bbrc.2012.08.002
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发表时间：
2012-09-07
影响因子：
3.1
通讯作者：
Huang, Shin-Hai
中科院分区：
文献类型：
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作者：
Lee, Wan-Chi;Wong, Hau-Yang;Huang, Shin-Hai
4-羟基壬烯醛（4-HNE）是在ω-6多不饱和脂肪酸的脂质过氧化过程中产生的主要醛。最近，4-HNE已被报道有助于神经元疾病如阿尔茨海默病的发病机制。然而，4-HNE在缺血性脑卒中中的作用尚不清楚。在本研究中，我们发现，血浆4-HNE浓度较高的遗传性卒中易感大鼠（卒中易感自发性高血压大鼠）和实验性脑卒中大鼠大脑中动脉闭塞（MCAO）。此外，MCAO术前静脉注射4-HNE不仅扩大了脑缺血诱导的梗死面积，而且增加了脑组织的氧化应激，表现为ROS/MPA水平升高，GSH/GSSG比值和MnSOD水平降低。过表达醛脱氢酶bcl-2（ALDH 2），一种催化4-HNE的酶，在PC 12细胞中挽救了对4-HNE处理的神经元存活。缺血性中风患者血浆4-HNE浓度高于对照组。在小样本人群（N = 60）中，血浆4-HNE浓度与血浆同型半胱氨酸浓度呈正相关，后者是缺血性卒中的危险因素。总之，我们的研究表明，血浆4-HNE水平是缺血性卒中的潜在生物标志物。(C)2012 Elsevier Inc. All rights reserved.
4-hydroxynonenal (4-HNE) is a major aldehyde produced during the lipid peroxidation of omega-6 polyunsaturated fatty acids. Recently, 4-HNE has been reported to contribute to the pathogenesis of neuronal diseases such as Alzheimer's disease. However, the role of 4-HNE in ischemic stroke is unclear yet. In this study, we found that plasma 4-HNE concentrations were higher in the genetic stroke-prone rats (stroke-prone spontaneously hypertensive rats) and experimental stroke rats with middle cerebral artery occlusion (MCAO). Moreover, administration of 4-HNE via intravenous injection before MCAO surgery not only enlarged cerebral ischemia-induced infarct area, but also increased oxidative stress in brain tissue, which was evidenced by the enhanced ROS/MPA levels, and the reduced GSH/GSSG ratio and MnSOD levels. Overexpression of aldehyde dehydrogenasesbcl-2 (ALDH2), an enzyme catalyses 4-HNE, rescued neuronal survival against 4-HNE treatment in PC12 cells. The plasma 4-HNE concentrations in patients with ischemic stroke were higher than those in control subjects. In a small sample population (N = 60), the plasma 4-HNE concentration was positively correlated with the plasma homocysteine concentration, a risk factor for ischemic stroke. Taken together, our study suggests that the plasma 4-HNE level is a potential biomarker for ischemic stroke. (C) 2012 Elsevier Inc. All rights reserved.