Department of Neurology, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.
Biochem Biophys Res Commun. 2012 Sep 7;425(4):842-7. doi: 10.1016/j.bbrc.2012.08.002. Epub 2012 Aug 7.
4-hydroxynonenal (4-HNE) is a major aldehyde produced during the lipid peroxidation of ω-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.
4-羟壬烯醛（4-HNE）是ω-6 多不饱和脂肪酸脂质过氧化过程中产生的主要醛类。最近，4-HNE 被报道有助于阿尔茨海默病等神经疾病的发病机制。然而，4-HNE 在缺血性中风中的作用尚不清楚。在这项研究中，我们发现血浆 4-HNE 浓度在遗传性中风易感大鼠（自发性高血压大鼠）和大脑中动脉闭塞（MCAO）实验性中风大鼠中较高。此外，在 MCAO 手术前通过静脉注射给予 4-HNE 不仅会扩大脑缺血引起的梗死面积，还会增加脑组织中的氧化应激，这表现为 ROS/MPA 水平升高，GSH/GSSG 比值和 MnSOD 水平降低。醛脱氢酶 bcl-2（ALDH2）是一种催化 4-HNE 的酶，其过表达可挽救 PC12 细胞免受 4-HNE 处理的神经元存活。缺血性中风患者的血浆 4-HNE 浓度高于对照组。在一个小样本人群（N=60）中，血浆 4-HNE 浓度与缺血性中风的危险因素血浆同型半胱氨酸浓度呈正相关。总之，我们的研究表明，血浆 4-HNE 水平是缺血性中风的一个潜在生物标志物。
