Liu Yang, Liang Jiang, Sha Zongge, Yang Changfu
School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
J Immunol Res. 2024 Feb 26;2024:9943747. doi: 10.1155/2024/9943747. eCollection 2024.
Rheumatoid arthritis (RA) is a chronic autoimmunity illness, mainly featured with synovitis of the joint. The specificity of ferroptosis is disparate in different diseases, and the mechanism of ferroptosis in RA has some uncertainty yet. Therefore, the mechanism of ferroptosis was deeply observed in RA patients and animal models. In this paper, plasma of RA patients, the tumor necrosis factor-alpha-induced human synovial fibroblasts, and an animal model of arthritis induced by collagen were applied to initially inquire about the therapeutic effect of ferroptosis. For the RA patients, ELISA detected protein expression of glutathione (GSH), GPX4, Nrf2, Keap-1, and ferritin. In cell experiments, erastin or fer-1 regulated the invasion of human synovial fibroblast cells, mitochondrial membrane potential, reactive oxygen species (ROS) expression, marker protein, and so on. For the animal experiments, 32 Sprague-Dawley male rats were randomly separated into four groups with a collagen-induced RA model for 14 days and administered with erastin or fer-1 for 35 days. The expressions of GSH, GPX4, Nrf2, and Keap-1 were lower, and the ferritin was higher in RA patients, and the expressions of these proteins varied significantly after disease remission. In addition, ferroptosis inactivation also reduced the proliferation and migration ability, mitochondrial membrane potential, and ROS in cells. We discovered unexpectedly that activation of ferroptosis meaningfully forbore the foot swelling in animals with CIA, reduced arthritis scores, destruction of bone, and articular synovitis, and also decreased the high expression of inflammatory factors in plasma. There is a nonlinear relationship between human disease manifestations and animal model pathology. Ferroptosis regulating in RA for humans or animals may produce different effects.
类风湿关节炎（RA）是一种慢性自身免疫性疾病，主要特征为关节滑膜炎。铁死亡在不同疾病中的特异性不同，RA中铁死亡的机制仍存在一定不确定性。因此，在RA患者和动物模型中深入观察了铁死亡的机制。本文应用RA患者血浆、肿瘤坏死因子-α诱导的人滑膜成纤维细胞以及胶原诱导的关节炎动物模型，初步探究铁死亡的治疗效果。对于RA患者，采用酶联免疫吸附测定法（ELISA）检测谷胱甘肽（GSH）、谷胱甘肽过氧化物酶4（GPX4）、核因子E2相关因子2（Nrf2）、 Kelch样ECH相关蛋白1（Keap-1）和铁蛋白的蛋白表达。在细胞实验中，使用埃拉司亭或铁死亡抑制剂1（fer-1）调节人滑膜成纤维细胞的侵袭、线粒体膜电位、活性氧（ROS）表达、标志物蛋白等。在动物实验中，将32只雄性Sprague-Dawley大鼠随机分为四组，采用胶原诱导RA模型14天，并用埃拉司亭或fer-1给药35天。RA患者中GSH、GPX4、Nrf2和Keap-1的表达较低，铁蛋白较高，疾病缓解后这些蛋白的表达有显著变化。此外，铁死亡失活也降低了细胞的增殖和迁移能力、线粒体膜电位以及ROS。我们意外地发现，铁死亡激活显著抑制了胶原诱导的关节炎（CIA）动物的足肿胀，降低了关节炎评分、骨破坏和关节滑膜炎，还降低了血浆中炎症因子的高表达。人类疾病表现与动物模型病理学之间存在非线性关系。对人类或动物RA进行铁死亡调节可能会产生不同的效果。
