| 硫酸氨基葡萄糖经SIRT1/GPX4信号通路改善膝骨关节炎的机制 |
| 投稿时间：2025-06-23 修订日期：2025-07-24 点此下载全文 |
| 引用本文：王刚,薛文娟,盖小雄,解达帅.硫酸氨基葡萄糖经SIRT1/GPX4信号通路改善膝骨关节炎的机制[J].医学研究杂志,2025,54(12):122-127 |
| DOI：
10.11969/j.issn.1673-548X.2025.12.021 |
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| 基金项目:山西省科学技术研究与开发项目(202202D731050) |
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| 中文摘要:目的 探讨硫酸氨基葡萄糖通过沉默信息调节因子2相关酶1/谷胱甘肽过氧化物酶4(silent mating type information regulation 2 homolog 1/glutathione peroxidase 4,SIRT1/GPX4)信号通路改善大鼠膝骨关节炎的作用机制。方法 选取SD大鼠36只,随机选取9只作为空白对照组,其余27只建立膝骨关节炎大鼠模型,失败2只,成功25只,然后进一步将其分为硫酸氨基葡萄糖组(n=8)、模型组(n=9)和硫酸氨基葡萄糖+EX-527组(n=8)。对比各组旷场实验、软骨组织病理学、铁死亡、内质网应激、软骨细胞凋亡率、骨组织代谢、软骨组织炎性细胞因子、自噬及SIRT1/GPX4信号通路表达情况。结果 与模型组、硫酸氨基葡萄糖+EX-527组比较,硫酸氨基葡萄糖组微管相关蛋白1轻链3BⅡ/Ⅰ(microtubule-associated protein 1 light chain 3BⅡ/Ⅰ,LC3BⅡ/Ⅰ)、Ⅰ型胶原C末端肽(C-terminal telopeptide of type Ⅰ collagen,CTX-Ⅰ)、旷场实验结果、UNC-51样激酶1(UNC-51 like kinase 1,ULK1)、骨钙素(osteocalcin,OCN)、自噬效应蛋白1(Beclin-1)、GPX4、SIRT1表达水平升高,C/EBP同源蛋白(C/EBP homologous protein,CHOP)、内质网应激、p62表达、凋亡率、铁死亡指标、炎性细胞因子表达水平下降(P<0.05)。结论硫酸氨基葡萄糖可抑制软骨细胞铁死亡来改善大鼠膝骨关节炎,减少内质网应激,改善骨代谢,减轻软骨细胞凋亡及炎性反应,促进软骨细胞自噬,其机制可能与调节SIRT1/GPX4信号通路相关。 |
| 中文关键词:硫酸氨基葡萄糖 沉默信息调节因子2相关酶1/谷胱甘肽过氧化物酶4信号通路 软骨细胞 铁死亡 膝骨关节炎 |
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| Mechanism of Glucosamine Sulfate Improve Knee Osteoarthritis through SIRT1/GPX4 Signaling Pathway. |
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| Abstract:Objective To investigate the mechanism of glucosamine sulfate improves knee osteoarthritis in rats through the silent mating type information regulation 2 homolog 1/glutathione peroxidase 4 (SIRT1/GPX4) signaling pathway. Methods Thirty-six rats were selected, and 9 rats were randomly selected as the blank control group, and the remaining 27 rats were established as knee osteoarthritis rat models, with 2 failured and 25 successed, which were further divided into the glucosamine sulfate group (n=8),the model group (n=9), and the glucosamine sulfate+EX-527 group (n=8). The open field test, cartilage histopathology, ferroptosis, endoplasmic reticulum stress, chondrocyte apoptosis rate, bone tissue metabolism, cartilage tissue inflammatory factors, autophagy and SIRT1/GPX4 signaling pathway expression were compared among each group. Results Compared with the model group and the glucosamine sulfate +EX-527 group, the microtubule-associated protein 1 light chain 3BⅡ/Ⅰ (LC3BⅡ/Ⅰ), C-terminal telopeptide of type Ⅰ collagen (CTX-Ⅰ), open field test results, UNC-51 like kinase 1 (ULK1), osteocalcin (OCN), Beclin-1, GPX4 and SIRT1 expression levels were increased in the glucosamine sulfate group, and C/EBP homologous protein (CHOP), endoplasmic reticulum stress, p62 expression, apoptosis rate, ferroptosis index and inflammatory factors expression levels were decreased (P<0.05). ConclusionGlucosamine sulfate inhibits ferroptosis of chondrocytes to improve knee osteoarthritis in rats, reduce endoplasmic reticulum stress, improves bone metabolism, attenuates chondrocyte apoptosis and inflammatory response, and promotes chondrocyte autophagy, the mechanism of which may be related to the regulation of the SIRT1/GPX4 signaling pathway. |
| keywords:Glucosamine sulfate Silent information regulator 2-related enzyme 1/glutathione peroxidase 4 signaling pathway Chondrocytes Ferroptosis Knee osteoarthritis |
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