Volume 10 Issue 3
May  2019
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Chen Xinpei, Su Song, Zhou Pengcheng, et al. MiR-494 alleviates hepatic ischemia-reperfusion injury in rats by activating PI3K/AKT signaling pathway[J]. ORGAN TRANSPLANTATION, 2019, 10(3): 295-301. doi: 10.3969/j.issn.1674-7445.2019.03.012
Citation: Chen Xinpei, Su Song, Zhou Pengcheng, et al. MiR-494 alleviates hepatic ischemia-reperfusion injury in rats by activating PI3K/AKT signaling pathway[J]. ORGAN TRANSPLANTATION, 2019, 10(3): 295-301. doi: 10.3969/j.issn.1674-7445.2019.03.012

MiR-494 alleviates hepatic ischemia-reperfusion injury in rats by activating PI3K/AKT signaling pathway

doi: 10.3969/j.issn.1674-7445.2019.03.012
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  • Corresponding author: Su Song, Email: 13882778554@163.com
  • Received Date: 2019-02-08
    Available Online: 2021-01-19
  • Publish Date: 2019-05-15
  •   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.

     

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  • [1]
    陈宝鹤, 李文美.乌司他丁联合缺血预处理对大鼠肝缺血再灌注损伤的影响[J].临床肝胆病杂志, 2018, 34(2):368-372.DOI: 10.3969/j.issn.1001-5256.2018.02.030.

    CHENG BH, LI WM. Effect of ulinastatin combined with ischemic preconditioning on hepatic ischemia-reperfusion injury in rats[J]. J Clin Hepatol, 2018, 34(2):368-372. DOI: 10.3969/j.issn.1001-5256.2018.02.030.
    [2]
    THEODORAKI K, ARKADOPOULOS N, NASTOS C, et al. Small liver remnants are more vulnerable to ischemia/reperfusion injury after extended hepatectomies: a case-control study[J]. World J Surg, 2012, 36(12):2895-2900. DOI: 10.1007/s00268-012-1779-6.
    [3]
    JEONG JS, KIM D, KIM KY, et al. Ischemic preconditioning produces comparable protection against hepatic ischemia/reperfusion injury under isoflurane and sevoflurane anesthesia in rats[J]. Transplant Proc, 2017, 49(9):2188-2193. DOI: 10.1016/j.transproceed.2017.07.002.
    [4]
    KATSUMI H, FUKUI K, SATO K, et al. Pharmacokinetics and preventive effects of platinum nanoparticles as reactive oxygen species scavengers on hepatic ischemia/reperfusion injury in mice[J]. Metallomics, 2014, 6(5):1050-1056. DOI: 10.1039/c4mt00018h.
    [5]
    ZHANG T, ZHAO Q, YE F, et al. Alda-1, an ALDH2 activator, protects against hepatic ischemia/reperfusion injury in rats via inhibition of oxidative stress[J]. Free Radic Res, 2018, 52(6):629-638. DOI: 10.1080/10715762.2018.1459042.
    [6]
    MANNE NDPK, ARVAPALLI R, GRAFFEO VA, et al. Prophylactic treatment with cerium oxide nanoparticles attenuate hepatic ischemia reperfusion injury in Sprague Dawley rats[J]. Cell Physiol Biochem, 2017, 42(5):1837-1846. DOI: 10.1159/000479540.
    [7]
    STRIFLER G, TUBOLY E, SZÉL E, et al. Inhaled methane limits the mitochondrial electron transport chain dysfunction during experimental liver ischemia-reperfusion injury[J]. PLoS One, 2016, 11(1):e0146363. DOI: 10.1371/journal.pone.0146363.
    [8]
    HAN SJ, JANG HS, SEU SY, et al. Hepatic ischemia/reperfusion injury disrupts the homeostasis of kidney primary cilia via oxidative stress[J]. Biochim Biophys Acta Mol Basis Dis, 2017, 1863(7):1817-1828. DOI: 10.1016/j.bbadis.2017.05.004.
    [9]
    BARTEL DP. MicroRNAs: genomics, biogenesis, mechanism, and function[J]. Cell, 2004, 116(2):281-297. doi: 10.1016/S0092-8674(04)00045-5
    [10]
    SHIVDASANI RA. MicroRNAs: regulators of gene expression and cell differentiation[J]. Blood, 2006, 108(12):3646-3653. doi: 10.1182/blood-2006-01-030015
    [11]
    YU CH, XU CF, LI YM. Association of microRNA-223 expression with hepatic ischemia/reperfusion injury in mice[J]. Dig Dis Sci, 2009, 54(11):2362-2366. DOI: 10.1007/s10620-008-0629-8.
    [12]
    CHEN Q, KONG L, XU X, et al. Down-regulation of microRNA-146a in the early stage of liver ischemia-reperfusion injury[J]. Transplant Proc, 2013, 45(2):492-496. DOI: 10.1016/j.transproceed.2012.10.045.
    [13]
    FARID WR, PAN Q, VAN DER MEER AJ, et al. Hepatocyte-derived microRNAs as serum biomarkers of hepatic injury and rejection after liver transplantation[J]. Liver Transpl, 2012, 18(3):290-297. DOI: 10.1002/lt.22438.
    [14]
    LI X, YI S, DENG Y, et al. MiR-124 protects human hepatic L02 cells from H2O2-induced apoptosis by targeting Rab38 gene[J]. Biochem Biophys Res Commun, 2014, 450(1):148-153. DOI: 10.1016/j.bbrc.2014.05.085.
    [15]
    LI L, LI G, YU C, et al. A role of microRNA-370 in hepatic ischaemia-reperfusion injury by targeting transforming growth factor-β receptor Ⅱ[J]. Liver Int, 2015, 35(4):1124-1132. DOI: 10.1111/liv.12441.
    [16]
    ZHAI F, ZHANG X, GUAN Y, et al. Expression profiles of microRNAs after focal cerebral ischemia/reperfusion injury in rats[J]. Neural Regen Res, 2012, 7(12):917-923. DOI: 10.3969/j.issn.1673-5374.2012.12.007.
    [17]
    WANG X, ZHANG X, REN XP, et al. MicroRNA-494 targeting both proapoptotic and antiapoptotic proteins protects against ischemia/reperfusion-induced cardiac injury[J]. Circulation, 2010, 122(13):1308-1318. DOI: 10.1161/CIRCULATIONAHA.110.964684.
    [18]
    李慧, 汪根树, 郑俊, 等.Zwint高表达对肝癌细胞增殖和肝癌肝移植预后的影响[J].器官移植, 2018, 9(2):122-129.DOI: 10.3969/j.issn.1674-7445.2018.02.006.

    LI H, WANG GS, ZHENG J, et al. Effect of high expression of Zwint on the proliferation of hepatoma cells and the prognosis of liver transplantation for hepatocellular carcinoma[J].Organ Transplant, 2018, 9(2):122-129.DOI: 10.3969/j.issn.1674-7445.2018.02.006.
    [19]
    ZAZUETA C, BUELNA-CHONTAL M, MACÍAS-LÓPEZ A, et al. Cytidine-5' -diphosphocholine protects the liver from ischemia/reperfusion injury preserving mitochondrial function and reducing oxidative stress[J]. Liver Transpl, 2018, 24(8):1070-1083. DOI: 10.1002/lt.25179.
    [20]
    LIU Y, LAI L, CHEN Q, et al. MicroRNA-494 is required for the accumulation and functions of tumor-expanded myeloid-derived suppressor cells via targeting of PTEN[J]. J Immunol, 2012, 188(11):5500-5510. DOI: 10.4049/jimmunol.1103505.
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