内皮细胞损伤是先兆子痫（PE）的一个重要特征。人脐带间充质干细胞来源的细胞外囊泡（HUMSC 来源的 EV）已被证明对多种疾病和组织损伤具有治疗作用。然而，HUMSC 衍生的 EV 对 PE 内皮损伤的治疗作用仍不清楚。本研究探讨了 HUMSC 衍生的 EV 治疗内皮细胞损伤的可能机制。采用肿瘤坏死因子α和脂多糖诱导的内皮功能障碍模型来评估 HUMSC 衍生的 EV 对内皮损伤的治疗效果。我们进一步构建了 PE 小鼠模型来探索 HUMSC 衍生的 EV 在体内的功能。通过代谢组学分析分析 HUMSC 来源的 EV 处理后内皮细胞代谢物的变化，并通过细胞实验进一步验证。 HUMSC 衍生的 EV 治疗可以减轻 PE 中的内皮细胞损伤，包括细胞增殖、迁移、血管生成和抗炎。重要的是，给予 HUMSC 衍生的 EV 可改善 PE 小鼠的高血压和蛋白尿，减轻肾脏损伤，并促进胎盘中的血管化。此外，代谢组学分析发现，在 HUMSC 衍生的 EV 处理后，精氨酸代谢途径被激活。我们还观察到精氨酸水平、一氧化氮含量和一氧化氮合酶活性增加，进一步的实验证明激活精氨酸代谢途径可以缓解内皮功能障碍。我们的结果表明，HUMSCs 衍生的 EV 可以通过激活精氨酸代谢途径改善 PE 内皮功能障碍，并可能作为治疗 PE 的一种治疗方法。

Endothelial cell damage is an important feature of preeclampsia (PE). Human umbilical mesenchymal stem-cell-derived extracellular vesicles (HUMSCs-derived EVs) have been shown to have therapeutic effects on a variety of diseases and tissue damage. However, the therapeutic effect of HUMSCs-derived EVs on endothelial injury in PE remains unclear. This study explored the possible mechanism of HUMSCs-derived EVs in the treatment of endothelial cell injury. Tumor necrosis factor α- and lipopolysaccharide-induced endothelial dysfunction models were used to evaluate the therapeutic effect of HUMSCs-derived EVs on endothelial injury. We further constructed PE mouse models to explore the function of HUMSCs-derived EVs in vivo. The changes of metabolites in endothelial cells after HUMSCs-derived EVs treatment were analyzed by metabolomics analysis and further validated by cell experiments. HUMSCs-derived EVs treatment can alleviate endothelial cell injury in PE, involving cell proliferation, migration, angiogenesis, and anti-inflammatory. Importantly, administration of HUMSCs-derived EVs improves hypertension and proteinuria in PE mice, alleviates kidney damage, and promotes vascularization in the placenta. Furthermore, metabolomics analysis found that the arginine metabolic pathway is activated after HUMSCs-derived EVs treatment. We also observed increased arginine level, nitric oxide content, and nitric oxide synthase activity, and further experiments proved that activating the arginine metabolic pathway could alleviate endothelial dysfunction. Our results reveal that HUMSCs-derived EVs could ameliorate PE endothelial dysfunction by activating the arginine metabolic pathway and may serve as a therapeutic method for treating PE.