Although liver ischaemia–reperfusion (I/R) injury remains the primary underlying reason for liver transplant failure or post-transplantation liver dysfunction, the underlying mechanism is still largely elusive. MicroRNAs (miRNA) are involved in multiple physiological and pathological processes, including inflammation. Here, we identified that the miR-128-3p/Rho family GTPase 3 (Rnd3)/NF‐κB axis might play a critical role in liver I/R injury. Our results demonstrated that the level of miR-128-3p was negatively correlated with the Rnd3 level during liver I/R. Dual luciferase reporter assay results proved that Rnd3 mRNA was a direct target of miR-128-3p. Additionally, Western blotting and quantitative RT-PCR analyses revealed that knock-down of miR-128-3p could up-regulate Rnd3 mRNA and protein levels, thereby suppressing the NF-κB pathway through down-regulating NF‐κB p65. Consequently, the serum levels of NF-κB–associated inflammatory factors and aspartate aminotransferase/alanine aminotransferase were decreased. Moreover, overexpression of Rnd3 could reverse the activation of NF-κB caused by miR-128-3p agomir during liver I/R injury. Overall, our study results suggest that repression of miR-128-3p can alleviate liver I/R injury through the miR-128-3p/Rnd3/NF‐κB axis and may facilitate the development of novel protective approaches against liver I/R injury.

尽管肝脏缺血-再灌注 (I/R) 损伤仍然是肝移植失败或移植后肝功能障碍的主要原因，但其潜在机制在很大程度上仍然难以捉摸。MicroRNA (miRNA) 参与多种生理和病理过程，包括炎症。在这里，我们发现 miR-128-3p/Rho 家族 GTPase 3 (Rnd3)/NF-κB 轴可能在肝 I/R 损伤中起关键作用。我们的结果表明，在肝脏 I/R 期间，miR-128-3p 的水平与 Rnd3 水平呈负相关。双荧光素酶报告基因检测结果证明 Rnd3 mRNA 是 miR-128-3p 的直接靶标。此外，蛋白质印迹和定量 RT-PCR 分析表明，敲低 miR-128-3p 可以上调 Rnd3 mRNA 和蛋白质水平，从而通过下调 NF-κB p65 抑制 NF-κB 通路。因此，NF-κB 相关炎症因子和天冬氨酸氨基转移酶/丙氨酸氨基转移酶的血清水平降低。此外，Rnd3 的过表达可以逆转肝脏 I/R 损伤期间由 miR-128-3p agomir 引起的 NF-κB 的激活。总的来说，我们的研究结果表明，抑制 miR-128-3p 可以通过 miR-128-3p/Rnd3/NF-κB 轴减轻肝脏 I/R 损伤，并可能促进针对肝脏 I/R 损伤的新型保护方法的开发.