目的 研究间充质干细胞来源外泌体（mesenchymal stem cell‑derived exosome, MSC‑Exo）是否通过调控JAK2/STAT3信号通路调节铁死亡以减轻缺氧复氧（hypoxia/re‑oxygenation, H/R）诱导的少突胶质细胞损伤。 方法 将少突胶质细胞随机分为对照组、H/R组和MSC‑Exo组，除对照组外，其余细胞均进行H/R处理。应用Western blot法检测少突胶质细胞标志物（MAG、Olig2、MOG、MBP）、外泌体标志物（TSG101、CD81、CD63）、内质网蛋白（calnexin）、铁死亡相关蛋白（GPX4、TFR）和JAK2/STAT3信号通路相关蛋白（JAK2、p‑JAK2、STAT3、p‑STAT3）的蛋白表达水平；采用CCK‑8法检测细胞活力；应用分光光度法检测胱天蛋白酶‑3活性、谷胱甘肽（glutathione, GSH）、Fe²⁺含量和丙二醛（malondialdehyde, MDA）水平；运用流式细胞术检测细胞凋亡水平和活性氧（reactive oxygen species, ROS）活性。为验证MSC‑Exo是否通过JAK2/STAT3信号通路抑制铁死亡，应用JAK2抑制剂（JAK2 inhibitor, JAK2i）后，将少突胶质细胞随机分为H/R组、MSC‑Exo组、JAK2i组和JAK2i+MSC‑Exo组。应用上述检测方法分别检测GPX4、TFR、p‑JAK2和p‑STAT3的蛋白表达水平，以及细胞活力、GSH、Fe²⁺含量、MDA水平、细胞凋亡水平和ROS活性情况。 结果 与对照组相比，H/R组细胞活力和GSH含量降低，ROS活性、MDA含量、Fe²⁺含量和细胞凋亡升高，H/R组TFR、p‑JAK2和p‑STAT3蛋白表达水平升高，GPX4蛋白水平降低（P<0.05）；与H/R组相比，JAK2i组和MSC‑Exo组均可抑制p‑JAK2、p‑STAT3和TFR蛋白表达水平，上调GPX4蛋白水平，提高细胞活力和GSH含量，降低MDA、Fe²⁺含量，抑制ROS活性和细胞凋亡的发生（P<0.05）。 结论 MSC‑Exo可通过抑制JAK2/STAT3信号通路抑制铁死亡的发生，减轻H/R诱导的少突胶质细胞损伤。

Objective To investigate whether mesenchymal stem cell-derived exosomes (MSC‑Exo) regulate ferroptosis by modulating the JAK2/STAT3 signaling pathway to alleviate hypoxia/re-oxygenation (H/R)-induced oligodendrocyte injury. Methods Oligodendrocytes were randomly divided into control, H/R, and MSC‑Exo groups. Except for the control group, cells underwent H/R treatment. Western blot analysis was used to detect protein expression of oligodendrocyte markers (MAG, Olig2, MOG, MBP), exosome markers (TSG101, CD81, CD63), endoplasmic reticulum protein (calnexin), ferroptosis-related proteins (GPX4, TFR), and JAK2/STAT3 signaling pathway components (JAK2, p-JAK2, STAT3, p-STAT3). Cell viability was assessed by CCK-8 assay. Spectrophotometric methods were employed to measure caspase-3 activity, glutathione (GSH) content, Fe²⁺ levels, and malondialdehyde (MDA) concentrations. Apoptosis and reactive oxygen species (ROS) production were analyzed by flow cytometry using Annexin-V/PI double staining. To verify the role of JAK2/STAT3 pathway in MSC‑Exo-mediated inhibition of ferroptosis, a JAK2 inhibitor (JAK2i) was applied, and cells were assigned to H/R, MSC‑Exo, JAK2i, and JAK2i + MSC‑Exo groups. The protein expression levels of GPX4, TFR, p-JAK2, and p-STAT3, as well as cell viability, GSH, Fe²⁺, MDA, apoptosis, and ROS production, were determined using the aforementioned methods. Results Compared with the control group, the H/R group showed significantly decreased cell viability and GSH content, and increased ROS, MDA, Fe²⁺, and apoptosis (P<0.05). Protein levels of TFR, p-JAK2, and p-STAT3 were significantly upregulated, while GPX4 was downregulated (P<0.05). Compared with the H/R group, both JAK2i and MSC‑Exo treatments significantly inhibited p-JAK2, p-STAT3, and TFR expression, upregulated GPX4 expression, increased cell viability and GSH content, and reduced ROS, MDA, Fe²⁺, and apoptosis levels (P<0.05). Conclusions MSC‑Exo inhibit ferroptosis by suppressing the JAK2/STAT3 signaling pathway, thereby alleviating H/R-induced oligodendrocyte injury.