| Quote
: |
彭俊, 彭清华, 吕怡, 熊晨, 陈向东, 罗琪.基于Keap1/Nrf2/HO-1通路探讨青光安Ⅱ号方对青光眼小鼠铁死亡的影响[J].湖南中医药大学学报英文版,2026,46(7):1303-1311.[Click to copy
] |
|
| |
|
|
| This paper
：Browser 99times Download 56times |
| 基于Keap1/Nrf2/HO-1通路探讨青光安Ⅱ号方对青光眼小鼠铁死亡的影响 |
| 彭俊,彭清华,吕怡,熊晨,陈向东,罗琪 |
| (湖南中医药大学, 湖南 长沙 410208;湖南中医药大学第一附属医院, 湖南 长沙 410007) |
| 摘要: |
| 目的 探讨青光安Ⅱ号方通过Kelch样ECH关联蛋白1（Keap1）/核因子E2相关因子2（Nrf2）/血红素氧合酶-1（HO-1）通路对青光眼小鼠铁死亡的影响及作用机制。方法 选取8只C57BL/6J小鼠作为空白组，40只自发性慢性高眼压DBA/2J青光眼小鼠随机分为模型组、青光安Ⅱ号方低剂量组、青光安Ⅱ号方中剂量组、青光安Ⅱ号方高剂量组、阳性药组，每组8只。空白组、模型组用等量蒸馏水灌胃，青光安Ⅱ号方低（9.75 g/kg）、中（19.5 g/kg）、高（39 g/kg）剂量组用青光安Ⅱ号方水煎液灌胃，阳性药组以30 μg/kg注射用鼠神经生长因子肌内注射，均连续干预28 d。监测小鼠眼压；HE染色观察视网膜组织形态及视网膜神经节细胞（RGCs）数量；Western blot检测Keap1、Nrf2、HO-1蛋白表达水平；DHE染色检测活性氧（ROS）含量；ELISA检测丙二醛（MDA）、超氧化物歧化酶（SOD）含量；亚铁离子（Fe2+）测定试剂盒检测Fe2+含量。结果 与空白组比较，模型组小鼠Keap1蛋白表达水平、ROS平均荧光强度、MDA及Fe2+含量升高（P<0.05），RGCs数量、SOD含量、Nrf2、HO-1的蛋白与mRNA表达水平下降（P<0.05）。与模型组比较，各给药组小鼠RGCs数量、Nrf2及HO-1 mRNA表达水平升高（P<0.05）；青光安Ⅱ号方中、高剂量组Keap1蛋白表达水平、ROS平均荧光强度、MDA及Fe2+含量下降（P<0.05），SOD含量、Nrf2蛋白表达水平升高（P<0.05）；青光安Ⅱ号方高剂量组HO-1蛋白表达水平升高（P<0.05）；阳性药组Keap1蛋白表达水平、ROS平均荧光强度、MDA及Fe2+含量下降（P<0.05），HO-1、Nrf2蛋白表达水平升高（P<0.05）。与青光安Ⅱ号方低剂量组比较，青光安Ⅱ号方中剂量组RGCs数量及Nrf2、HO-1 mRNA表达水平升高（P<0.05）；青光安Ⅱ号方高剂量组、阳性药组Keap1蛋白表达水平、ROS平均荧光强度、Fe2+含量下降（P<0.05），RGCs数量、Nrf2蛋白与mRNA表达水平、HO-1 mRNA表达水平升高（P<0.05）；阳性药组MDA含量下降（P<0.05）。与青光安Ⅱ号方中剂量组比较，青光安Ⅱ号方高剂量组ROS平均荧光强度、Fe2+含量下降（P<0.05），Nrf2 mRNA表达水平升高（P<0.05）；阳性药组ROS平均荧光强度下降（P<0.05），Nrf2及HO-1 mRNA表达水平升高（P<0.05）。与青光安Ⅱ号方高剂量组比较，阳性药组ROS平均荧光强度上升（P<0.05），Nrf2及HO-1 mRNA表达水平升高（P<0.05）。结论 青光安Ⅱ号方可能通过抑制Keap1、激活Nrf2/HO-1通路，减轻小鼠视网膜组织氧化应激、抑制铁死亡，保护视神经，且呈一定的剂量依赖性，以青光安Ⅱ号方高剂量组效果最优。 |
| 关键词: 青光眼|青光安Ⅱ号方|Kelch样ECH关联蛋白1|核因子E2相关因子2|血红素氧合酶-1|铁死亡 |
| DOI：10.3969/j.issn.1674-070X.2026.07.001 |
| Received:June 03, 2026 |
| 基金项目:国家自然科学基金项目（82274588，82575150）；湖南省自然科学基金高校联合基金重点项目（2025JJ90004）；2025年湖南省医学学科B类建设项目（湘卫医发〔2025〕7号）；湖南中医药大学科研基金“揭榜挂帅”项目（2022XJJB003）；湖南中医药大学研究生科研创新项目（2025CX050）。 |
|
| Effects of Qingguang'an Ⅱ Formula on ferroptosis in glaucoma mice based on the Keap1/Nrf2/HO-1 pathway |
| PENG Jun, PENG Qinghua, LYU Yi, XIONG Chen, CHEN Xiangdong, LUO Qi |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To explore the effects and mechanism of action of Qingguang'an Ⅱ Formula on ferroptosis in glaucoma mice through the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Methods Eight C57BL/6J mice were selected as the blank group, and 40 spontaneous chronic ocular hypertensive DBA/2J glaucoma mice were randomly divided into model group, the Qingguang'an Ⅱ Formula low-, medium-, and high-dose groups, and positive drug group, with 8 mice in each group. The blank and model groups received equal volumes of distilled water by gavage; the Qingguang'an Ⅱ Formula low- (9.75 g/kg), medium- (19.5 g/kg), and high-dose (39 g/kg) groups received Qingguang'an Ⅱ Formula decoction by gavage; the positive drug group received mouse nerve growth factor for injection intramuscularly at 30 μg/kg. All interventions lasted for 28 consecutive days. Intraocular pressure of mice was monitored; retinal histomorphology and retinal ganglion cell (RGC) counts were observed by HE staining; Keap1, Nrf2, and HO-1 protein expression levels were determined by Western blot; reactive oxygen species (ROS) content was measured by DHE staining; malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured by ELISA; ferrous ion (Fe2+) content was determined using Fe2+ assay kit. Results Compared with the blank group, the model group showed increased Keap1 protein expression, mean ROS fluorescence intensity, MDA and Fe2+ levels (P<0.05), and decreased RGC counts, SOD levels, as well as Nrf2 and HO-1 protein and mRNA expression levels (P<0.05). Compared with the model group, all treatment groups showed increased RGC counts, Nrf2, and HO-1 mRNA expression levels (P<0.05); the Qingguang'an Ⅱ Formula medium- and high-dose groups showed decreased Keap1 protein expression levels, mean ROS fluorescence intensity, MDA and Fe2+ levels (P<0.05), and increased SOD levels and Nrf2 protein expression levels (P<0.05); the Qingguang'an Ⅱ Formula high-dose group showed increased HO-1 protein expression levels (P<0.05); the positive drug group showed decreased Keap1 protein expression levels, mean ROS fluorescence intensity, MDA and Fe2+ levels (P<0.05), and increased HO-1 and Nrf2 protein expression levels (P<0.05). Compared with the Qingguang'an Ⅱ Formula low-dose group, the medium-dose group showed increased RGC counts, Nrf2 and HO-1 mRNA expression levels (P<0.05); the high-dose group and positive drug group showed decreased Keap1 protein expression levels, mean ROS fluorescence intensity, and Fe2+ levels (P<0.05), and increased RGC counts, Nrf2 protein and mRNA expression levels, and HO-1 mRNA expression levels (P<0.05); the positive drug group showed decreased MDA levels (P<0.05). Compared with the Qingguang'an Ⅱ Formula medium-dose group, the high-dose group showed decreased mean ROS fluorescence intensity and Fe2+ levels (P<0.05) and increased Nrf2 mRNA expression levels (P<0.05); the positive drug group showed decreased mean ROS fluorescence intensity (P<0.05) and increased Nrf2 and HO-1 mRNA expression levels (P<0.05). Compared with the Qingguang'an Ⅱ Formula high-dose group, the positive drug group showed increased mean ROS fluorescence intensity (P<0.05) and increased Nrf2 and HO-1 mRNA expression levels (P<0.05). Conclusion Qingguang'an Ⅱ Formula may attenuate oxidative stress, inhibit ferroptosis, and protect the optic nerve in mouse retinal tissues by suppressing Keap1 and activating the Nrf2/HO-1 pathway. These effects show a certain dose-dependency, with the high-dose Qingguang'an Ⅱ group demonstrating the optimal efficacy. |
| Key words: glaucoma|Qingguang'an Ⅱ Formula|Kelch-like ECH-associated protein 1|nuclear factor erythroid 2-related factor 2|heme oxygenase-1|ferroptosis |
|
二维码（扫一下试试看！） |
|
|
|
|
