Neurosurgery Department, The Third People's Hospital of Henan Province, Zhongyuan District, Zhengzhou City, Henan Province, China.
Nuclear Medicine Department, The First Affiliated Hospital of Zhengzhou University, Erqi District, Zhengzhou City, Henan Province, China.
J Cell Mol Med. 2024 Feb;28(3):e18089. doi: 10.1111/jcmm.18089. Epub 2023 Dec 25.
Endothelial dysfunction is an independent risk factor for stroke. The dysfunction of endothelial cells (EC) is closely concerned with EC senescence. Gastrodin (GAS) is an organic compound extracted from the dried root mass of the Orchidaceae plant Gastrodiae gastrodiae. It is used clinically to treat diseases such as vertebrobasilar insufficiency, vestibular neuronitis and vertigo. In the present study, we used hydrogen peroxide (H O )-induced human umbilical vein endothelial cells (HUVECs) to establish an in vitro EC senescence model and to investigate the role and mechanism of GAS in EC senescence. It's found that H O -treated HUVECs increased the proportion of senescence-associated β-galactosidase (SA β-gal) positive cells and the relative protein expression levels of senescence-associated cyclin p16 and p21. In addition, GAS reduced the proportion of SA β-gal positive cells and the relative protein expression levels of p16 and p21, and increased the proliferation and migration ability of HUVECs. Meanwhile, GAS increased the expression of the anti-oxidative stress protein HO-1 and its nuclear expression level of Nrf2. The anti-senescence effect of GAS was blocked when HO-1 expression was inhibited by SnPPIX. Furthermore, absence of HO-1 abolished the effect of GAS on HUVEC proliferation and migration. In conclusion, GAS ameliorated H O -induced cellular senescence and enhanced cell proliferation and migration by enhancing Nrf2/HO-1 signalling in HUVECs. These findings of our study expanded the understanding of GAS pharmacology and suggested that GAS may offer a potential therapeutic agent for stroke.
内皮功能障碍是中风的独立危险因素。内皮细胞（EC）的功能障碍与 EC 衰老密切相关。天麻素（GAS）是从兰科植物天麻的干燥根茎中提取的有机化合物。临床上用于治疗椎基底动脉供血不足、前庭神经元炎、眩晕等疾病。本研究采用过氧化氢（H2O2）诱导人脐静脉内皮细胞（HUVEC）建立体外 EC 衰老模型，探讨 GAS 对 EC 衰老的作用及机制。结果表明，H2O2 处理后的 HUVECs 中衰老相关β-半乳糖苷酶（SA β-gal）阳性细胞比例及衰老相关 cyclin p16 和 p21 的相对蛋白表达水平增加。GAS 降低了 SA β-gal 阳性细胞的比例及 p16 和 p21 的相对蛋白表达水平，增加了 HUVECs 的增殖和迁移能力。同时，GAS 增加了抗氧化应激蛋白 HO-1 的表达及其核转录因子 Nrf2 的核表达水平。用 SnPPIX 抑制 HO-1 表达可阻断 GAS 的抗衰老作用。此外，缺乏 HO-1 可消除 GAS 对 HUVEC 增殖和迁移的作用。综上所述，GAS 通过增强 HUVEC 中的 Nrf2/HO-1 信号通路，改善了 H2O2 诱导的细胞衰老，增强了细胞增殖和迁移。本研究结果扩展了对 GAS 药理学的认识，并提示 GAS 可能为中风提供一种潜在的治疗药物。
