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论著 | 更新时间:2026-03-18
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大豆黄酮对氢醌诱导的干性年龄相关性黄斑变性模型小鼠的保护作用研究▲
Study on the protective effect of daidzien on mouse models of hydroquinone-induced dry age-related macular degeneration

微创医学 页码:27-33

作者机构:南宁爱尔眼科医院眼底科,广西南宁市 530000

基金信息:广西自然科学基金项目(编号:2025GXNSFAA069182);广西壮族自治区卫生健康委员会自筹经费科研课题(编号:Z-A20251080);湖南省创新型省份建设自然科学基金(编号:2023JJ70050) *通信作者 欧足国为共同通信作者

DOI:10.11864/j.issn.1673.2026.01.04

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  • 英文简介
  • 参考文献

目的 探讨大豆黄酮对氢醌诱导的干性年龄相关性黄斑变性(AMD)模型小鼠的保护作用。方法 将60只小鼠按随机数字表法分为对照组、模型组、大豆黄酮高剂量组、大豆黄酮低剂量组,每组15只。给予模型组、大豆黄酮高剂量组、大豆黄酮低剂量组小鼠含0.8%氢醌的饮用水饲养;给予对照组小鼠常规饮用水饲养。同时,给予大豆黄酮高剂量组小鼠10 mg/kg大豆黄酮(生理盐水溶解)灌胃,给予大豆黄酮低剂量组小鼠5 mg/kg大豆黄酮(生理盐水溶解)灌胃,模型组和对照组小鼠同时给予等体积生理盐水灌胃。3个月后,利用Micron Ⅳ小动物视网膜成像系统对4组小鼠行眼底视网膜成像,取出小鼠右眼球用于透射电子显微镜检查,摘左眼球取血并取出眼球用于酶联免疫吸附试验检测。结果 眼底视网膜成像结果显示,与对照组小鼠相比,模型组小鼠的视网膜厚度下降,视网膜各个层次结构遭到破坏,布鲁赫膜内出现大量的玻璃膜疣,表明干性AMD小鼠模型构建成功。与模型组小鼠比较,大豆黄酮低剂量组小鼠视网膜厚度未见明显变化,仍可观察到玻璃膜疣;大豆黄酮高剂量组小鼠视网膜厚度有明显改善且接近对照组小鼠,可见不规则布鲁赫膜,少见玻璃膜疣。眼底透射电子显微镜检查结果显示,与对照组小鼠相比,模型组小鼠视网膜结构不清晰,黑色素颗粒含量减少,布鲁赫膜发生了明显的变形,提示发生干性AMD样病变;与模型组小鼠相比,大豆黄酮低剂量组小鼠视网膜结构无明显改善,布鲁赫膜相对规则,黑色素颗粒密度增多;与大豆黄酮低剂量组相比,大豆黄酮高剂量组小鼠布鲁赫膜规则,黑色素颗粒密度高。与对照组小鼠相比,模型组、大豆黄酮低剂量组、大豆黄酮高剂量组小鼠眼球组织丙二醛表达水平升高,且模型组升高幅度更明显,模型组、大豆黄酮低剂量组、大豆黄酮高剂量组小鼠眼球组织超氧化物歧化酶、谷胱甘肽、过氧化氢酶表达水平降低,且模型组小鼠降低幅度更明显(P<0.05);大豆黄酮高剂量组小鼠眼球组织谷胱甘肽、过氧化氢酶表达水平高于大豆黄酮低剂量组(P<0.05)。与对照组小鼠相比,模型组、大豆黄酮低剂量组、大豆黄酮高剂量组小鼠血清丙二醛表达水平升高,且模型组小鼠升高幅度更明显,模型组小鼠血清超氧化物歧化酶、谷胱甘肽、过氧化氢酶表达水平下降,大豆黄酮低剂量组小鼠血清谷胱甘肽、过氧化氢酶表达水平下降(P<0.05);与模型组小鼠相比,大豆黄酮低剂量组小鼠血清谷胱甘肽、过氧化氢酶表达水平升高,大豆黄酮高剂量组小鼠血清超氧化物歧化酶、谷胱甘肽、过氧化氢酶表达水平升高(P<0.05);大豆黄酮高剂量组小鼠血清过氧化氢酶表达水平高于大豆黄酮低剂量组(P<0.05)。结论 大豆黄酮可能通过减轻视网膜色素上皮细胞的氧化应激损伤从而发挥对干性AMD小鼠的保护作用。

Objective To investigate the protective effect of daidzein on mouse models of hydroquinone-induced dry age-related macular degeneration (AMD). Methods Sixty mice were randomly divided into a control group, a model group, a high-dose daidzein group and a low-dose daidzein group by the random number table method, with 15 mice in each group. Mice in the model group, high-dose daidzein group and low-dose daidzein group were given drinking water containing 0.8% hydroquinone, whereas mice in the control group were given conventional drinking water. Meanwhile, mice in the high-dose daidzein group were intragastrically administered 10 mg/kg daidzein dissolved in physiological saline, and those in the low-dose daidzein group were intragastrically administered 5 mg/kg daidzein dissolved in physiological saline. Mice in the model group and control group were given an equal volume of physiological saline by gavage at the same time. After 3 months, fundus retinal imaging was performed in mice of the four groups using the Micron Ⅳ retinal imaging system for small animals. The right eyeballs of the mice were harvested for transmission electron microscopy. The left eyeballs were enucleated for blood collection, and the isolated left eyeballs were subjected to enzyme-linked immunosorbent assay. Results Fundus retinal imaging showed that compared with the control group, the retinal thickness of the model group was decreased, the layered structure of the retina was damaged, and a large number of drusen were present in the Bruch's membrane, indicating the successful establishment of the dry AMD mouse model. Compared with the model group, the retinal thickness showed no significant change in the low-dose daidzein group, and drusen were still observable. In the high-dose daidzein group, the retinal thickness was significantly improved and close to that of the control group, with the irregular Bruch's membrane and rare drusen observed. Transmission electron microscopy of the fundus revealed that compared with the control group, the model group showed unclear retinal structure, decreased melanin granule content, and obvious deformation of the Bruch's membrane, suggesting the occurrence of dry AMD-like lesions. Compared with the model group, the low‑dose daidzein group showed no significant improvement in retinal structure, with the relatively regular Bruch's membrane and increased density of melanin granules. Compared with the low-dose daidzein group, the high‑dose daidzein group exhibited the regular Bruch's membrane and a higher density of melanin granules. Compared with the control group, the expression levels of malondialdehyde in ocular tissue were significantly increased in the model group, low-dose daidzein group and high-dose daidzein group, with a more marked increase in the model group. The expression levels of superoxide dismutase, glutathione and catalase in ocular tissue were significantly decreased in the model group, low-dose daidzein group and high-dose daidzein group, with a more pronounced reduction in the model group (P<0.05). The expression levels of glutathione and catalase in the high-dose daidzein group were significantly higher than those in the low-dose daidzein group (P<0.05). Compared with the control group, the serum expression levels of malondialdehyde were increased in the model group, low-dose daidzein group and high-dose daidzein group, with a more marked increase in the model group. The serum expression levels of superoxide dismutase, glutathione and catalase were decreased in the model group, and the serum expression levels of glutathione and catalase were decreased in the low-dose daidzein group (P<0.05). Compared with the model group, the serum expression levels of glutathione and catalase were increased in the low-dose daidzein group, and the serum expression levels of superoxide dismutase, glutathione and catalase were increased in the high-dose daidzein group (P<0.05). The serum expression level of catalase in the high-dose daidzein group was higher than that in the low-dose daidzein group (P<0.05). Conclusion Daidzein may exert a protective effect on mice with dry AMD by alleviating oxidative stress injury in retinal pigment epithelial cells.

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