Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) expressing microRNAs have been highlighted in human diseases. However, the detailed molecular mechanism of hucMSCs-derived exosomal miR-18b-3p on preeclampsia (PE) remains further investigation. We aimed to investigate the effect of exosomes and miR-18b-3p/leptin (LEP) on occurrence of PE. The morphology of the hucMSC and hucMSC-exosomes (Exos) was identified. The exosomes were infected with different lentivirus expressing miR-18b-3p to explore the role of miR-18b-3p in PE. The PE rat model was established by intraperitoneal injection of N-nitro-l-arginine methyl ester. The expression of LEP and miR-18b-3p was tested in PE rat placenta tissues. Also, the effect of exosomes on LEP and miR-18b-3p expression was detected. The systolic blood pressure (SBP), proteinuria, inflammatory factors, the weight of fetal rat and placenta and cell apoptosis in PE rats were detected. Finally, the relationship between miR-18b-3p and LEP was verified using dual-luciferase reporter gene assay and RNA pull-down assay. Exosomes, restoring miR-18b-3p or inhibiting LEP reduced SBP and proteinuria of PE rats as well as increased the weight of fetal rat and placenta, decreased serum levels of inflammatory factors as well as suppressed apoptotic cells of PE rats, exerting a suppressive effect on PE progression. miR-18b-3p was decreased and LEP was increased in placenta tissues of PE rats. LEP was the direct target gene of miR-18b-3p. Upregulation of miR-18b-3p or treatment of the exosomes suppressed LEP expression and reduced PE occurrence, while downregulation of miR-18b-3p had contrary effects. Downregulated LEP reversed the effect of miR-18b-3p reduction on PE rats. HucMSCs-derived exosomal miR-18b-3p targets LEP to participate in the occurrence and development of PE. This study may provide a novel theoretical basis for the mechanism and investigation of PE.

源自表达 microRNA 的人脐带间充质干细胞 (hucMSC) 的外泌体已在人类疾病中得到强调。然而，hucMSCs 衍生的外泌体 miR-18b-3p 对先兆子痫 (PE) 的详细分子机制仍有待进一步研究。我们旨在研究外泌体和 miR-18b-3p/leptin (LEP) 对 PE 发生的影响。鉴定了 hucMSC 和 hucMSC-外泌体 (Exos) 的形态。外泌体感染表达miR-18b-3p的不同慢病毒以探索miR-18b-3p在PE中的作用。通过腹腔注射N-硝基-l建立PE大鼠模型-精氨酸甲酯。在 PE 大鼠胎盘组织中测试了 LEP 和 miR-18b-3p 的表达。此外，还检测了外泌体对 LEP 和 miR-18b-3p 表达的影响。检测PE大鼠收缩压（SBP）、蛋白尿、炎症因子、胎鼠及胎盘重量及细胞凋亡情况。最后，使用双荧光素酶报告基因分析和 RNA pull-down 分析验证了 miR-18b-3p 和 LEP 之间的关系。外泌体、恢复miR-18b-3p或抑制LEP可降低PE大鼠SBP和蛋白尿，增加胎鼠和胎盘重量，降低血清炎症因子水平，抑制PE大鼠凋亡细胞，发挥抑制作用关于 PE 进展。PE 大鼠胎盘组织中 miR-18b-3p 减少，LEP 增加。LEP是miR-18b-3p的直接靶基因。miR-18b-3p 的上调或外泌体的处理抑制了 LEP 表达并减少了 PE 的发生，而 miR-18b-3p 的下调具有相反的效果。下调 LEP 逆转了 miR-18b-3p 减少对 PE 大鼠的影响。HucMSCs来源的外泌体miR-18b-3p靶向LEP参与PE的发生发展。本研究可为PE的发生机制及研究提供新的理论依据。