Baicalin is an active compound extracted from Scutellaria baicalensis with antioxidant and anti‐inflammatory properties. Bone mesenchymal stem cells (BMSCs)‐derived exosomes have shown promise for the treatment of hepatic ischemia–reperfusion (I/R) injury. This study aims to investigate the role of Baicalin‐pretreated BMSCs‐derived exosomes in hepatic I/R injury and its mechanisms. BMSCs were pretreated with or without Baicalin, and their exosomes (Ba‐Exo and Exo) were collected and characterized. These exosomes were administered to mice via tail vein injection. Treatment with Exo and Ba‐Exo significantly suppressed the elevation of ALT and AST induced by hepatic injury. Additionally, both Exo and Ba‐Exo treatments resulted in a reduction in the liver weight‐to‐body weight ratio. RT‐PCR results revealed a significant downregulation of pro‐inflammatory cytokines with Exo and Ba‐Exo treatment. Both Exo and Ba‐Exo treatment improved the Th17/Treg cell imbalance induced by I/R and reduced hepatic injury. Additionally, exosomes were cocultured with normal liver cells, and the expression of fibroblast growth factor 21 (FGF21) in liver cells was elevated through Ba‐Exo treatment. After treatment, the JAK2/STAT3 pathway was inhibited, and FOXO1 expression was upregulated. Finally, recombinant FGF21 was injected into mouse tail veins to assess its effects. Recombinant FGF21 injection further inhibited the JAK2/STAT3 pathway, increased FOXO1 expression, and improved the Th17/Treg cell imbalance. In conclusion, this study confirms the protective effects of Exo and Ba‐Exo against hepatic I/R injury. Ba‐Exo mitigates hepatic I/R injury, achieved through inducing FGF21 expression in liver cells, inhibiting the JAK2/STAT3 pathway, and activating FOXO1 expression. Therefore, baicalin pretreatment emerges as a promising strategy to enhance the therapeutic capability of BMSCs‐derived exosomes for hepatic I/R.

中文翻译：

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黄芩苷预处理的骨髓间充质干细胞衍生的外泌体通过 FGF21 和 JAK2/STAT3 通路改善肝缺血再灌注后 Th17/Treg 失衡

黄芩苷是从黄芩苷中提取的活性化合物黄芩具有抗氧化和抗炎特性。骨间充质干细胞（BMSC）来源的外泌体已显示出治疗肝缺血再灌注（I/R）损伤的前景。本研究旨在探讨黄芩苷预处理的骨髓间充质干细胞来源的外泌体在肝缺血再灌注损伤中的作用及其机制。使用或不使用黄芩苷对 BMSC 进行预处理，并收集并表征其外泌体（Ba-Exo 和 Exo）。这些外泌体通过尾静脉注射给予小鼠。Exo 和 Ba-Exo 治疗显着抑制肝损伤引起的 ALT 和 AST 升高。此外，Exo 和 Ba-Exo 治疗均导致肝脏重量与体重之比降低。RT-PCR 结果显示，Exo 和 Ba-Exo 治疗显着下调促炎细胞因子。Exo 和 Ba-Exo 治疗均改善了 I/R 引起的 Th17/Treg 细胞失衡，并减少了肝损伤。此外，将外泌体与正常肝细胞共培养，通过Ba-Exo处理，肝细胞中成纤维细胞生长因子21（FGF21）的表达升高。治疗后，JAK2/STAT3通路受到抑制，FOXO1表达上调。最后，将重组FGF21注射到小鼠尾静脉中以评估其效果。重组FGF21注射进一步抑制JAK2/STAT3通路，增加FOXO1表达，改善Th17/Treg细胞失衡。总之，本研究证实了 Exo 和 Ba-Exo 对肝 I/R 损伤的保护作用。Ba-Exo 通过诱导肝细胞中 FGF21 表达、抑制 JAK2/STAT3 通路并激活 FOXO1 表达来减轻肝 I/R 损伤。因此，黄芩苷预处理成为增强 BMSC 来源的外泌体治疗肝 I/R 能力的有前景的策略。