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大豆异黄酮拮抗β-淀粉样肽诱导的大鼠神经元线粒体氧化损伤。

Antagonizing effects of soybean isoflavones on β-amyloid peptide-induced oxidative damage in neuron mitochondria of rats.

机构信息

Department of Nutrition & Food Hygiene, School of Public Health and Family Medicine, Capital Medical University, Beijing, China.

出版信息

Basic Clin Pharmacol Toxicol. 2012 Oct;111(4):248-53. doi: 10.1111/j.1742-7843.2012.00900.x.

Abstract

Soybean isoflavone (SIF) has been demonstrated to have neuroprotective effects induced by β-amyloid peptides (Aβ) through suppressing oxidative stress; however, the explicit mechanisms still remain uncovered. In the present study, 32 Wistar rats were randomly divided into four groups: an Aβ1-42-treated group, a SIF + Aβ1-42 group, a SIF-treated group and a control group. We measured the protein content of 8-hydroxydeoxyguanosine (8-OhdG) and mRNA expression of 8-oxoguanine DNA glycosylase (OGG1). The protein expression of OGG1, Bcl-xl, Bad, beta subunit of ATP synthase (ATPB) and pyruvate dehydrogenase (PDH) in brain was also measured. The results showed that the level of 8-OHdG in both SIF groups was significantly decreased compared to the Aβ1-42-treated group (p < 0.05), while the mRNA and protein expression of OGG1 in the SIF + Aβ1-42 groups were up-regulated compared with the Aβ1-42-treated groups (p < 0.05). The expression of Bcl-xl was up-regulated in the SIF-treated group compared with the Aβ1-42-treated groups (p < 0.05), while the expression of Bad was down-regulated in the two SIF-treated groups (p < 0.05). Aβ1-42 significantly down-regulated the expression of ATPase and PDH proteins compared with the control group (p < 0.05). SIF reversed the down-regulation effects on the mitochondrial energy metabolic enzymes induced by Aβ1-42 (p < 0.05) in the rats. These results suggest that SIF alleviate the oxidative stress in neurons and mitochondria of rat brains mediated by Aβ1-42, and these protective effects might be associated with the regulation of OGG1, Bad, Bcl-xl, ATPB and PDH.

摘要

大豆异黄酮(SIF)已被证明通过抑制氧化应激对β-淀粉样肽(Aβ)具有神经保护作用;然而,其明确的机制仍未被揭示。在本研究中,32 只 Wistar 大鼠被随机分为四组:Aβ1-42 处理组、SIF+Aβ1-42 组、SIF 处理组和对照组。我们测量了 8-羟基脱氧鸟苷(8-OhdG)的蛋白含量和 8-氧鸟嘌呤 DNA 糖基化酶(OGG1)的 mRNA 表达。还测量了大脑中 OGG1、Bcl-xl、Bad、三磷酸腺苷合酶(ATPB)β亚基和丙酮酸脱氢酶(PDH)的蛋白表达。结果显示,与 Aβ1-42 处理组相比,SIF 两组的 8-OHdG 水平均显著降低(p<0.05),而 SIF+Aβ1-42 组的 OGG1 mRNA 和蛋白表达均高于 Aβ1-42 处理组(p<0.05)。与 Aβ1-42 处理组相比,SIF 处理组的 Bcl-xl 表达上调(p<0.05),而两组 SIF 处理组的 Bad 表达下调(p<0.05)。与对照组相比,Aβ1-42 显著下调了 ATP 酶和 PDH 蛋白的表达(p<0.05)。SIF 逆转了 Aβ1-42 诱导的大鼠脑线粒体能量代谢酶的下调作用(p<0.05)。这些结果表明,SIF 减轻了 Aβ1-42 介导的大鼠神经元和线粒体中的氧化应激,这些保护作用可能与 OGG1、Bad、Bcl-xl、ATPB 和 PDH 的调节有关。

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