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柏雪烨紫, 高文文, 王得春, 朱斌, 刘心竹, 龚嘎蓝孜.芒柄花素调控HIF-2α/EPO信号通路改善慢性高原病大鼠的红细胞过度增多[J].湖南中医药大学学报,2026,46(6):1089-1095[点击复制] |
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| 芒柄花素调控HIF-2α/EPO信号通路改善慢性高原病大鼠的红细胞过度增多 |
| 柏雪烨紫,高文文,王得春,朱斌,刘心竹,龚嘎蓝孜 |
| (西藏大学医学院, 西藏 拉萨 850000;西藏军区总医院, 西藏 拉萨 850000) |
| 摘要: |
| 目的 基于缺氧诱导因子-2α（HIF-2α）/红细胞生成素（EPO）信号通路，探究芒柄花素对慢性高原病大鼠红细胞过度增多的影响。方法 将60只雄性SD大鼠随机分为对照组、模型组、芒柄花素低剂量组、芒柄花素中剂量组、芒柄花素高剂量组、芒柄花素高剂量+HIF-2α稳定剂FG-4592组（简称FG-4592组），每组10只。测定各组大鼠的肺动脉压，测定外周血的红细胞计数、血红蛋白、红细胞压积指标，检测血清中EPO、丙二醛（MDA）、超氧化物歧化酶（SOD）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）的水平，Western blot检测肾脏组织中HIF-2α（核）、EPO及骨髓组织中GATA结合蛋白-1（GATA-1）、磷酸化促红细胞生成素受体（p-EPOR）蛋白的表达。结果 与对照组比较，模型组大鼠的肺动脉压、红细胞计数、血红蛋白、红细胞压积、EPO、HIF-2α、GATA-1、p-EPOR、MDA、IL-6、TNF-α水平升高（P<0.05），SOD水平降低（P<0.05）；与模型组比较，芒柄花素低、中、高剂量组大鼠的肺动脉压、红细胞计数、血红蛋白、红细胞压积、EPO、HIF-2α、GATA-1、p-EPOR、MDA、IL-6、TNF-α水平降低（P<0.05），SOD水平升高（P<0.05）；与芒柄花素高剂量组比较，FG-4592组的肺动脉压、红细胞计数、血红蛋白、红细胞压积、EPO、HIF-2α、GATA-1、p-EPOR、MDA、IL-6、TNF-α水平升高（P<0.05），SOD水平降低（P<0.05）。结论 芒柄花素能够抑制慢性高原病大鼠红细胞过度生成，同时减轻红细胞异常增殖所介导的氧化应激及炎症反应，其机制可能与抑制HIF-2α/EPO信号通路有关。 |
| 关键词: 芒柄花素 慢性高原病 HIF-2α/EPO信号通路 红细胞增多 氧化应激 炎症 |
| DOI：10.3969/j.issn.1674-070X.2026.06.001 |
| 投稿时间：2026-04-17 |
| 基金项目:国家自然科学基金资助项目（U22A20340）；西藏自治区科技计划项目（XZ202502JD0027）。 |
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| Formononetin regulates the HIF-2α/EPO pathway to ameliorate excessive erythrocytosis in rats with chronic mountain sickness |
| BAI Xueyezi, GAO Wenwen, WANG Dechun, ZHU Bin, LIU Xinzhu, GONGGA Lanzi |
| (Medical College, Xizang University, Lhasa, Xizang 850000, China;General Hospital of Xizang Military Region, Lhasa, Xizang 850000, China) |
| Abstract: |
| Objective To investigate the effects of formononetin on excessive erythrocytosis in rats with chronic mountain sickness (CMS) based on the hypoxia inducible factor-2α (HIF-2α)/erythropoietin (EPO) signaling pathway. Methods Sixty male SD rats were randomly divided into control group, model group, low-, medium-, and high-dose formononetin groups, as well as formononetin high-dose+HIF-2α stabilizer FG-4592 group (FG-4592 group), with 10 rats in each group. Pulmonary arterial pressure was measured in each group of rats. Red blood cell count (RBC), hemoglobin (Hb), and hematocrit (HCT) of the peripheral blood were determined. Serum levels of EPO, malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured. Western blot was performed to determine the protein expression of nuclear HIF-2α and EPO in kidney tissues, as well as GATA-binding protein-1 (GATA-1) and phosphorylated erythropoietin receptor (p-EPOR) in bone marrow tissues. Results Compared with the control group, the model group showed increases in pulmonary arterial pressure, RBC, Hb, HCT, EPO, HIF-2α, GATA-1, p-EPOR, MDA, IL-6, and TNF-α (P<0.05), and a decreased SOD level (P<0.05). Compared with the model group, the formononetin low-, medium-, and high-dose groups exhibited decreases in pulmonary arterial pressure, RBC, Hb, HCT, EPO, HIF-2α, GATA-1, p-EPOR, MDA, IL-6, and TNF-α (P<0.05), and an increase in SOD level (P<0.05). Compared with the formononetin high-dose group, the FG-4592 group showed elevations in pulmonary arterial pressure, RBC, Hb, HCT, EPO, HIF-2α, GATA-1, p-EPOR, MDA, IL-6, and TNF-α (P<0.05), and a decrease in SOD level (P<0.05). Conclusion Formononetin can inhibit excessive erythrocyte production in rats with CMS and simultaneously alleviate the oxidative stress and inflammatory responses mediated by abnormal erythrocyte proliferation. Its mechanism may be related to the inhibition of the HIF-2α/EPO signaling pathway. |
| Key words: formononetin chronic mountain sickness HIF-2α/EPO signaling pathway erythrocytosis oxidative stress inflammation |
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