ABSTRACT

Isoflurane has been studied in ischemia-reperfusion injury, while the regulatory mechanism by which isoflurane regulates microRNA(miR)-9-3p in hepatic ischemia/reperfusion injury (HIRI) via targeting fibronectin type III domain containing 3B (FNDC3B) remains seldom investigated. This study aims to determine the role of miR-9-3p in HIRI progression under the treatment of isoflurane. Rat HIRI models were established and treated with isoflurane. MiR-9-3p was altered to assess its role in inflammation, oxidative stress, transaminases, pathology, and hepatocyte apoptosis in HIRI rat liver tissues. Expression of miR-9-3p and FNDC3B in rat liver tissues was determined, and the targeting relationship between miR-9-3p and FNDC3B was confirmed using bioinformatic prediction and dual luciferase reporter gene assay. MiR-9-3p was downregulated, whereas FNDC3B was upregulated in HIRI rat liver tissues. Isoflurane treatment upregulated miR-9-3p and attenuated pathological changes, inflammation, oxidative stress, transaminases, and hepatocyte apoptosis in HIRI rat liver tissues. MiR-9-3p upregulation further strengthened the effect of isoflurane on HIRI, while miR-9-3p downregulation suppressed the therapeutic role of isoflurane. FNDC3B was confirmed as a target gene of miR-9-3p. Isoflurane upregulates miR-9-3p to protect rats from HIRI by inhibiting FNDC3VB. Our research may provide novel targets for HIRI treatment.

摘要

异氟烷已在缺血再灌注损伤中进行了研究，而异氟烷通过靶向含有 3B 的纤连蛋白 III 型结构域 (FNDC3B) 调节肝缺血/再灌注损伤 (HIRI) 中的 microRNA(miR)-9-3p 的调节机制仍然很少研究。本研究旨在确定 miR-9-3p 在异氟醚治疗下 HIRI 进展中的作用。建立大鼠 HIRI 模型并用异氟醚处理。改变 MiR-9-3p 以评估其在 HIRI 大鼠肝组织中的炎症、氧化应激、转氨酶、病理学和肝细胞凋亡中的作用。测定大鼠肝组织中miR-9-3p和FNDC3B的表达，并通过生物信息学预测和双荧光素酶报告基因分析证实miR-9-3p和FNDC3B之间的靶向关系。MiR-9-3p 被下调，而 FNDC3B 在 HIRI 大鼠肝组织中上调。异氟醚治疗上调 miR-9-3p 并减弱 HIRI 大鼠肝组织的病理变化、炎症、氧化应激、转氨酶和肝细胞凋亡。MiR-9-3p 上调进一步加强了异氟醚对 HIRI 的作用，而 miR-9-3p 下调则抑制了异氟醚的治疗作用。FNDC3B被确认为miR-9-3p的靶基因。异氟醚通过抑制 FNDC3VB 上调 miR-9-3p 以保护大鼠免受 HIRI。我们的研究可能为 HIRI 治疗提供新的靶点。MiR-9-3p 上调进一步加强了异氟醚对 HIRI 的作用，而 miR-9-3p 下调则抑制了异氟醚的治疗作用。FNDC3B被确认为miR-9-3p的靶基因。异氟醚通过抑制 FNDC3VB 上调 miR-9-3p 以保护大鼠免受 HIRI。我们的研究可能为 HIRI 治疗提供新的靶点。MiR-9-3p 上调进一步加强了异氟醚对 HIRI 的作用，而 miR-9-3p 下调则抑制了异氟醚的治疗作用。FNDC3B被确认为miR-9-3p的靶基因。异氟醚通过抑制 FNDC3VB 上调 miR-9-3p 以保护大鼠免受 HIRI。我们的研究可能为 HIRI 治疗提供新的靶点。