目的 研究大豆异黄酮对缺血性脑卒中的保护作用及潜在作用机制。方法 从大豆Glycine max中分离大豆异黄酮并进行成分分析。构建氧糖剥夺/再灌注（oxygen glucose deprivation/reperfusion，OGD/R）诱导的PC12细胞模型，考察大豆异黄酮对细胞存活率、迁移能力、凋亡及细胞内Ca²⁺、活性氧（reactive oxygen species，ROS）、乳酸脱氢酶（lactate dehydrogenase，LDH）、半胱氨酸天冬氨酸蛋白酶-3（cystein-asparate protease-3，Caspase-3）水平和Kelch样环氧氯丙烷相关蛋白1（Kelch-like ECH-associated protein 1，Keap1）/核因子E2相关因子2（nuclear factor erythroid 2-related factor 2，Nrf2）通路相关蛋白表达的影响。采用双侧颈总动脉结扎法建立大鼠全脑缺血再灌注损伤模型，考察大豆异黄酮对神经功能评分、脑组织含水量、脑梗死体积占比、脑组织病理变化及脑组织超氧化物歧化酶（superoxide dismutase，SOD）、谷胱甘肽过氧化物酶（glutathione peroxidase，GSH-Px）、过氧化氢酶（catalase，CAT）、LDH活性、丙二醛（malondialdehyde，MDA）水平和Keap1/Nrf2通路相关蛋白表达的影响。结果 体外实验结果显示，与模型组比较，大豆异黄酮显著提高细胞存活率和迁移率（P＜0.05、0.01），降低细胞凋亡率和细胞内Ca²⁺、ROS、LDH、Caspase-3水平（P＜0.05、0.01），上调Nrf2、血红素加氧酶-1（heme oxygenase-1，HO-1）、醌氧化还原酶1[NAD(P)H quinone oxidoreductase 1，NQO1]的蛋白表达（P＜0.01），下调Keap1蛋白表达（P＜0.05、0.01）。体内实验结果显示，与模型组比较，大豆异黄显著改善大鼠神经功能缺损、减轻脑水肿及梗死体积（P＜0.01），修复脑组织病理损伤，降低脑组织内MDA水平和LDH活性（P＜0.01），提高脑组织内SOD、CAT和GSH-Px活性（P＜0.01），上调脑组织Nrf2、HO-1和NQO1蛋白表达（P＜0.01），下调脑组织Keap1蛋白表达（P＜0.01）。结论 大豆异黄酮对缺血性脑卒中有显著的神经保护作用，其机制可能与通过激活Keap1/Nrf2通路，增强机体抗氧化能力、抑制氧化应激损伤、减少神经细胞凋亡及减轻脑组织损伤有关。

Objective To study the protective effect and potential mechanism of soybean isoflavones (SI) on ischemic stroke. Methods SI were isolated from soybeans and components were analyzed. An oxygen glucose deprivation/reperfusion (OGD/R)-induced PC12 cells model was constructed to investigate the effect of SI on cell survival, migration ability, apoptosis, intracellular Ca²⁺, reactive oxygen species (ROS), lactate dehydrogenase (LDH), cysteine aspartate protease-3 (Caspase-3) levels, and expressions of Kelch-like ECH associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway related proteins. A rat model of global cerebral ischemia-reperfusion injury was established using bilateral common carotid artery ligation. The effect of SI on neurological function score, brain tissue water content, proportion of cerebral infarction volume, pathological changes, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), LDH activities, malondialdehyde (MDA) level, and expressions of Keap1/Nrf2 pathway related proteins in brain tissue were investigated. Results In vitro experiments showed that compared with model group, SI significantly increased cell survival rate and migration rate (P < 0.05, 0.01), decreased cell apoptosis rate and intracellular Ca²⁺, ROS, LDH, Caspase-3 levels (P < 0.05, 0.01), upregulated Nrf2, heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1) protein expressions (P < 0.01), and downregulated Keap1 protein expression (P < 0.05, 0.01). In vivo experiments, compared with model group, SI significantly improved neurological deficits, reduced brain edema and infarct volume in rats (P < 0.01), repaired brain tissue pathological damage, reduced MDA level and LDH activity in brain tissue (P < 0.01), increased SOD, CAT and GSH-Px activities in brain tissue (P < 0.01), upregulated Nrf2, HO-1 and NQO1 protein expressions in brain tissue (P < 0.01), and downregulated Keap1 protein expression in brain tissue (P < 0.01). Conclusion SI have a significant neuroprotective effect on ischemic stroke, which may be related to the activation of Keap1/Nrf2 pathway, enhancing the antioxidant capacity of body, inhibiting oxidative stress damage, reducing neuronal apoptosis and alleviating brain tissue damage.

R285.5

吉林省自然科学基金资助项目（20260102166JC）；长春师范大学研究生创新项目（YJSCX2025119）