Wang Bailun, Gu Angran, Yan Jie, Zhang Yi, Liu Jifa, Sun Chang, Wei Yi, Gu Changping, Wang Yuelan
Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
Int Immunopharmacol. 2025 Jun 23;162:115130. doi: 10.1016/j.intimp.2025.115130.
Acute lung injury (ALI) is the most serious complication of sepsis, but there is currently a lack of effective treatment methods. Therefore, finding drugs to treat sepsis induced acute lung injury (SALI) is an urgent clinical problem that needs to be solved. Kaempferol has been proven to have therapeutic effects on various lung diseases. We used cecal ligation puncture (CLP) method to create a mouse model of sepsis. Mouse plasma exosomes and exosomes secreted by alveolar epithelial cells were injected into mice via tail vein, western blotting, PCR, flow cytometry, and other techniques were used to detect lung injury and macrophage activation in mice. Our research shows that the therapeutic effect of kaempferol in alleviating SALI partially depends on the extracellular vesicle mechanism. Compared with the Control group, the CLP group mice showed an increase in plasma exosome content, and these plasma exosomes gathered more in the lungs and promoted overactivation of alveolar macrophages. However, treatment with kaempferol reduced the levels of plasma exosomes in CLP mice and inhibited the harmful effects of exosomes on alveolar macrophages and lung tissue. Through biological information analysis and in vitro and in vivo experiments, we further discovered that the plasma exosomes affected by kaempferol exert their effects by inhibiting the MAPK signaling pathway, and these effects were amplified by MAPK inhibitors. And we found that the plasma exosomes affected by kaempferol come from alveolar epithelial cells. This study suggests that kaempferol can alleviate SALI by reducing the MAPK signaling pathway mediated by extracellular vesicles in alveolar epithelial cells and inhibiting macrophage activation.
急性肺损伤（ALI）是脓毒症最严重的并发症，但目前缺乏有效的治疗方法。因此，寻找治疗脓毒症诱导的急性肺损伤（SALI）的药物是一个亟待解决的临床问题。山奈酚已被证明对多种肺部疾病具有治疗作用。我们采用盲肠结扎穿刺（CLP）法建立脓毒症小鼠模型。将小鼠血浆外泌体和肺泡上皮细胞分泌的外泌体经尾静脉注入小鼠体内，运用蛋白质免疫印迹法、聚合酶链反应、流式细胞术等技术检测小鼠的肺损伤及巨噬细胞活化情况。我们的研究表明，山奈酚减轻SALI的治疗作用部分依赖于细胞外囊泡机制。与对照组相比，CLP组小鼠血浆外泌体含量增加，这些血浆外泌体在肺内聚集增多并促进肺泡巨噬细胞过度活化。然而，山奈酚治疗降低了CLP小鼠血浆外泌体水平，并抑制了外泌体对肺泡巨噬细胞和肺组织的有害作用。通过生物信息分析以及体外和体内实验，我们进一步发现，受山奈酚影响的血浆外泌体通过抑制丝裂原活化蛋白激酶（MAPK）信号通路发挥作用，且这些作用被MAPK抑制剂放大。并且我们发现，受山奈酚影响的血浆外泌体来源于肺泡上皮细胞。本研究提示，山奈酚可通过降低肺泡上皮细胞细胞外囊泡介导的MAPK信号通路并抑制巨噬细胞活化来减轻SALI。
