Department of Obstetrics and Gynecology, Xi'jing Hospital, 4th Military Medical University, 17 Changle Westroad, Xi'an 710032, People's Republic of China.
Br J Nutr. 2010 Nov;104(9):1297-303. doi: 10.1017/S0007114510002291. Epub 2010 Jun 28.
The present study was undertaken to investigate the antioxidant effect of chronic ingestion of genistein (Gen) against neural death in the brain of ovariectomised (Ovx) rats. The rats were randomly divided into five groups, i.e. sham-operated (sham), Ovx-only, Ovx with 17β-oestradiol, Ovx with low (15 mg/kg) and high (30 mg/kg) doses of Gen (Gen-L and Gen-H), and were orally administered daily with drugs or vehicle for 6 weeks. The learning and memory abilities were measured by Morris water maze test. Oxidative damages in the brain were evaluated by the level of superoxide dismutase (SOD), malondialdehyde (MDA) and monoamine oxidase (MAO) activities. Neural apoptosis was shown by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining and caspase-3 activity. In the visual learning and memory test, there were no significant differences among the population means of the five groups. While in the probe trial test, the Gen-L group instead of the Gen-H group exhibited reduced escape latency and increased memory frequency than the Ovx group. Although both doses of Gen could reduce acetylcholinesterase activity, only a low dose of Gen could diminish MDA activity significantly in frontal cortex and enhance SOD content in the hippocampus. In contrast, MAO content was decreased in the cortex by either dose of Gen, while in the hippocampus, only a high dose of Gen appeared to be effective. Interestingly, Gen at both the doses could attenuate the increased number of TUNEL-positive neurons and caspase-3 activity in Ovx rats. These results suggest that Gen confers protection against Ovx-induced neurodegeneration by attenuating oxidative stress, lipid peroxidation and the mitochondria-mediated apoptotic pathway in a region- and dose-dependent manner.
本研究旨在探讨长期摄入染料木黄酮（Gen）对去卵巢（Ovx）大鼠大脑神经死亡的抗氧化作用。将大鼠随机分为五组，即假手术（sham）、Ovx 组、Ovx 加 17β-雌二醇组、Ovx 加低（15mg/kg）和高（30mg/kg）剂量 Gen 组（Gen-L 和 Gen-H），并分别给予药物或载体口服 6 周。通过 Morris 水迷宫测试评估学习和记忆能力。通过超氧化物歧化酶（SOD）、丙二醛（MDA）和单胺氧化酶（MAO）活性水平评估大脑氧化损伤。通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）染色和 caspase-3 活性显示神经细胞凋亡。在视觉学习和记忆测试中，五组人群的平均值之间没有显著差异。然而，在探测试验中，Gen-L 组而非 Gen-H 组的逃避潜伏期缩短，记忆频率增加，与 Ovx 组相比。尽管两种剂量的 Gen 都可以降低乙酰胆碱酯酶活性，但只有低剂量的 Gen 可以显著降低额皮质中的 MDA 活性，并增加海马中的 SOD 含量。相反，两种剂量的 Gen 均可降低皮质中的 MAO 含量，但仅高剂量的 Gen 对海马有效。有趣的是，两种剂量的 Gen 都可以减轻 Ovx 大鼠中 TUNEL 阳性神经元数量的增加和 caspase-3 活性的增加。这些结果表明，Gen 通过减轻氧化应激、脂质过氧化和线粒体介导的凋亡途径，以剂量依赖的方式对 Ovx 诱导的神经退行性变提供保护。
