MiR-494 alleviates hepatic ischemia-reperfusion injury in rats by activating PI3K/AKT signaling pathway
10.3969/j.issn.1674-7445.2019.03.012
- VernacularTitle:MiR-494通过激活PI3K/AKT通路减轻大鼠肝缺血—再灌注损伤
- Author:
Xinpei CHEN
1
;
Song SU
;
Pengcheng ZHOU
;
De LUO
;
Xiangdong LIU
;
Anding LIU
;
Bo LI
Author Information
1. Department of Hepatobiliary Surgery, the Affliated Hospital of Southwest Medical University, Luzhou 646000, China
- Publication Type:Research Article
- Keywords:
MicroRNA;
MiR-494;
Hepatic ischemia-reperfusion injury;
PI3K/AKT signaling pathway;
Apoptosis;
Oxidative stress;
Liver transplantation
- From:
Organ Transplantation
2019;10(3):295-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and related mechanism of microRNA (miR)-494 on the hepatic ischemia-reperfusion injury (HIRI). Methods Twenty-four male SD rats were randomly divided into four groups (n=6 in each group). In the sham operation group, abdominal surgery without hepatic ischemia-reperfusion was performed. In the HIRI group, partial liver ischemia was performed for 60 min, followed by 6 h perfusion. In the HIRI+agomir-miR-494 group, intraperitoneal injection of agomir-miR-494 (20 μL) was daily given within preoperative 7 d. In HIRI+agomir-NC group, an equivalent quantity of agomir-NC was daily injected intraperitoneally within preoperative 7 d. The expression level of miR-494 messenger RNA(mRNA) in the liver tissues in each group was detected by reverse transcription polymerase chain reaction (RT-PCR). The expression levels of liver injury and oxidative stress related indexes were measured by relevant kits. The histopathological changes of the liver in each group were observed. The quantity of apoptotic cells and cytoplasmic histone-related DNA fragments in the liver tissues of rats was detected by relevant kits. The expression levels of the proteins related to the phosphatidylinositol-3-kinase(PI3K)/protein kinase(AKT) signaling pathway were measured by Western blot. Results The expression level of miR-494 mRNA in the rat liver tissues in the HIRI+agomir-miR-494 group was significantly higher than that in the HIRI+agomir-NC group (P < 0.01). The levels of the serum liver injury and oxidative stress related indexes in the HIRI+agomir-miR-494 group were significantly lower than those in the HIRI+agomir-NC group (all P < 0.01). Compared with those in the HIRI+agomir-NC group, the quantity of cellular necrosis was significantly reduced, the cell integrity was considerably increased and the quantity of TUNELpositive cells was evidently decreased in the HIRI+agomir-miR-494 group (all P < 0.05). The expression levels of poly ADP-ribose polymerase(PARP), cysteinyl aspartate specific proteinase-3(Caspase-3) and Bax in the HIRI+agomirmiR-494 group were significantly lower than those in the HIRI+agomir-NC group (all P < 0.05). The quantity of DNA fragments in the HIRI+agomir-miR-494 group was significantly less than that in the HIRI+agomir-NC group (P < 0.01). The expression levels of p-AKT, p-mammalian target of rapamycin(mTOR) and p-p70S6K in the HIRI+agomir-miR-494 group were significantly higher than those in the HIRI+agomir-NC group (all P < 0.05). Conclusions miR-494 can alleviate the severity of HIRI in rats by activating the PI3K/AKT signaling pathway.
