[1]曹平苏露煜 仝警安 张唯 韦玮.大黄素甲醚对糖尿病视网膜病变模型大鼠的保护作用及机制[J].现代中医药,2023,(06):089-95.[doi:10.13424/j.cnki.mtcm.2023.06.019]
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大黄素甲醚对糖尿病视网膜病变模型大鼠的保护作用及机制()
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《现代中医药》[ISSN:1006-6977/CN:61-1281/TN]

卷:
期数:
2023年06期
页码:
089-95
栏目:
出版日期:
2023-12-08

文章信息/Info

文章编号:
1672-0571(2023)06-0089-07
作者:
曹平1苏露煜1 仝警安1 张唯1 韦玮2
1.陕西中医药大学附属医院，陕西 咸阳 712000；
2.陕西中医药大学第一临床医学院，陕西 咸阳 712046
关键词:
关键词：大黄素甲醚; 糖尿病视网膜病变; 血管内皮生长因子; 细胞凋亡; 核因子红系2相关因子2; 磷酸化核因子-kappa B
分类号:
R255.4
DOI:
10.13424/j.cnki.mtcm.2023.06.019
文献标志码:
A
摘要:
摘 要：目的 探讨大黄素甲醚（physcion，PHY）对糖尿病视网膜病变（diabetic retinopathy，DR）大鼠的治疗作用及其可能机制。方法 将SPF级雄性SD大鼠分为5组（n=12）：空白组、模型组、PHY低剂量组、PHY中剂量组和PHY高剂量组，治疗4 w后，检测各组大鼠的空腹血糖（fasting plasma glucose，FPG）、糖化血红蛋白（glycosylated hemoglobin，HbA1c）、空腹胰岛素（fasting insulin，FINS）、白介素（interleukin,IL）-1β、IL-6和肿瘤坏死因子-α（Tumor necrosis factor-α，TNF-α）和视网膜超氧化物歧化酶（Superoxide dismutase，SOD）、过氧化氢酶（Catalase，CAT）、谷胱甘肽过氧化物酶（Glutathione peroxidase，GSH-PX）和丙二醛（Malondialdehyde，MDA）的水平；对大鼠视网膜进行苏木精和伊红（Hematoxylin and eosin，HE）染色和原位末端转移酶标记技术(TdT-mediated dUTP nick-end labeling,TUNEL)染色；分析视网膜BCL2相关X蛋白（BCL2 Associated X Protein，BAX）、B淋巴细胞瘤-2（BCL2）和血管内皮生长因子A（Vascular endothelial growth factor A，VEGFA）mRNA水平，视网膜细胞核核因子红系2相关因子2（Nuclear factor erythroid 2 related factor 2，NRF2）、Kelch样ECH关联蛋白1（Kelch like ECH associated protein 1，Keap1）和磷酸化核因子-kappa B p65（p-NF-κB p65）蛋白表达水平。结果 与空白组比较，模型组大鼠的FPG、HbA1c和FINS水平升高（P<0.05），视网膜中IL-1β、IL-6和TNF-α水平升高（P<0.05），视网膜中SOD、CAT和GSH-PX水平降低（P<0.05），视网膜中MDA水平升高（P<0.05）；视网膜出现明显病变，视网膜TUNEL阳性率以及BAX和VEGFA的mRNA水平升高（P<005），视网膜中BCL2的mRNA水平降低（P<005）；视网膜细胞核NRF2蛋白水平降低（P<0.05），Keap1和p-NF-κB p65蛋水平升高（P<0.05）。与模型组比较，PHY低剂量组、PHY中剂量组和PHY高剂量组大鼠的FPG、HbA1c和FINS水平降低（P<0.05），视网膜中IL-1β、IL-6和TNF-α水平降低（P<0.05），视网膜中SOD、CAT和GSH-PX水平升高（P<0.05），视网膜MDA水平降低（P<005）；视网膜病变减轻，视网膜中TUNEL阳性率以及BAX和VEGFA的mRNA水平降低（P<005），视网膜中BCL2对的mRNA水平升高（P<005）；视网膜细胞核NRF2蛋白水平升高（P<0.05），Keap1和p-NF-κB p65蛋白水平降低（P<0.05）。结论 大黄素甲醚可有效减轻DR大鼠视网膜损伤，其机制可能与抑制VEGF表达、NRF2介导的氧化应激和NF-κB介导的炎症反应有关。 摘 要：目的 探讨大黄素甲醚（physcion，PHY）对糖尿病视网膜病变（diabetic retinopathy，DR）大鼠的治疗作用及其可能机制。方法 将SPF级雄性SD大鼠分为5组（n=12）：空白组、模型组、PHY低剂量组、PHY中剂量组和PHY高剂量组，治疗4 w后，检测各组大鼠的空腹血糖（fasting plasma glucose，FPG）、糖化血红蛋白（glycosylated hemoglobin，HbA1c）、空腹胰岛素（fasting insulin，FINS）、白介素（interleukin,IL）-1β、IL-6和肿瘤坏死因子-α（Tumor necrosis factor-α，TNF-α）和视网膜超氧化物歧化酶（Superoxide dismutase，SOD）、过氧化氢酶（Catalase，CAT）、谷胱甘肽过氧化物酶（Glutathione peroxidase，GSH-PX）和丙二醛（Malondialdehyde，MDA）的水平；对大鼠视网膜进行苏木精和伊红（Hematoxylin and eosin，HE）染色和原位末端转移酶标记技术(TdT-mediated dUTP nick-end labeling,TUNEL)染色；分析视网膜BCL2相关X蛋白（BCL2 Associated X Protein，BAX）、B淋巴细胞瘤-2（BCL2）和血管内皮生长因子A（Vascular endothelial growth factor A，VEGFA）mRNA水平，视网膜细胞核核因子红系2相关因子2（Nuclear factor erythroid 2 related factor 2，NRF2）、Kelch样ECH关联蛋白1（Kelch like ECH associated protein 1，Keap1）和磷酸化核因子-kappa B p65（p-NF-κB p65）蛋白表达水平。结果 与空白组比较，模型组大鼠的FPG、HbA1c和FINS水平升高（P<0.05），视网膜中IL-1β、IL-6和TNF-α水平升高（P<0.05），视网膜中SOD、CAT和GSH-PX水平降低（P<0.05），视网膜中MDA水平升高（P<0.05）；视网膜出现明显病变，视网膜TUNEL阳性率以及BAX和VEGFA的mRNA水平升高（P<005），视网膜中BCL2的mRNA水平降低（P<005）；视网膜细胞核NRF2蛋白水平降低（P<0.05），Keap1和p-NF-κB p65蛋水平升高（P<0.05）。与模型组比较，PHY低剂量组、PHY中剂量组和PHY高剂量组大鼠的FPG、HbA1c和FINS水平降低（P<0.05），视网膜中IL-1β、IL-6和TNF-α水平降低（P<0.05），视网膜中SOD、CAT和GSH-PX水平升高（P<0.05），视网膜MDA水平降低（P<005）；视网膜病变减轻，视网膜中TUNEL阳性率以及BAX和VEGFA的mRNA水平降低（P<005），视网膜中BCL2对的mRNA水平升高（P<005）；视网膜细胞核NRF2蛋白水平升高（P<0.05），Keap1和p-NF-κB p65蛋白水平降低（P<0.05）。结论 大黄素甲醚可有效减轻DR大鼠视网膜损伤，其机制可能与抑制VEGF表达、NRF2介导的氧化应激和NF-κB介导的炎症反应有关。

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备注/Memo

备注/Memo:
基金项目：陕西省优秀中医药人才研修项目（陕中医药函【2022】102号）；陕西省重点研发计划（2017SF-350）；咸阳市科学技术研究计划项目（2015k04-17）
更新日期/Last Update: 2023-11-23