Huang Zuotian, Zheng Daofeng, Pu Junliang, Dai Jiangwen, Zhang Yuchi, Zhang Wanqiu, Wu Zhongjun
a Department of Hepatobiliary Surgery , The First Affiliated Hospital of Chongqing Medical University , Chongqing , China.
Biosci Biotechnol Biochem. 2019 May;83(5):829-835. doi: 10.1080/09168451.2019.1569495. Epub 2019 Jan 27.
MicroRNA-125b (miR-125b), which was previously proved to be a potential immunomodulator in various disease, attenuated mouse hepatic ischemia/reperfusion (I/R) injury in this study. miR-125b was decreased in RAW 264.7 cells exposed to hypoxia/reoxygenation (H/R). The expression of IL-1β, IL-6 and TNF-α in both serum and supernate were reduced in miR-125b over-expression groups. The hepatic histopathological changes were reduced in miR-125b agomir groups. In the miR-125b antagomir groups, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly elevated compared with negative control (NC) groups. The protein expression of TNF receptor-associated factor 6 (TRAF6), IL-1β and the phosphorylation of p65 (p-p65) were suppressed by the up-regulation of miR-125b. Furthermore, the nuclear translocation of p-p65, measured by immunofluorescence, was enhanced by the miR-125b inhibitors. In conclusion, our study indicates that miR-125b protects liver from hepatic I/R injury via inhibiting TRAF6 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signal pathway.
微小RNA-125b（miR-125b）先前已被证明在多种疾病中是一种潜在的免疫调节剂，在本研究中可减轻小鼠肝脏缺血/再灌注（I/R）损伤。在暴露于缺氧/复氧（H/R）的RAW 264.7细胞中，miR-125b水平降低。在miR-125b过表达组中，血清和上清液中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达均降低。在miR-125b激动剂组中，肝脏组织病理学变化减轻。在miR-125b拮抗剂组中，与阴性对照（NC）组相比，血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平显著升高。miR-125b的上调抑制了肿瘤坏死因子受体相关因子6（TRAF6）、IL-1β的蛋白表达以及p65的磷酸化（p-p65）。此外，通过免疫荧光检测发现，miR-125b抑制剂增强了p-p65的核转位。总之，我们的研究表明，miR-125b通过抑制TRAF6和活化B细胞核因子κB（NF-κB）信号通路保护肝脏免受肝I/R损伤。
