Volume 8 Issue 5
Sep.  2017
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Teng Xu, Ding Fan, Chen Wenjie, et al. High-dose sirolimus protects hepatic ischemia-reperfusion injury probably through promoting cellular autophagy in aged mice[J]. ORGAN TRANSPLANTATION, 2017, 8(5): 349-354. doi: 10.3969/j.issn.1674-7445.2017.05.003
Citation: Teng Xu, Ding Fan, Chen Wenjie, et al. High-dose sirolimus protects hepatic ischemia-reperfusion injury probably through promoting cellular autophagy in aged mice[J]. ORGAN TRANSPLANTATION, 2017, 8(5): 349-354. doi: 10.3969/j.issn.1674-7445.2017.05.003
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High-dose sirolimus protects hepatic ischemia-reperfusion injury probably through promoting cellular autophagy in aged mice

doi: 10.3969/j.issn.1674-7445.2017.05.003

  • The Sixth People' s Hospital of Longgang District of Shenzhen, Shenzhen 518117, China

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  • Corresponding author: Xu Chi, Email: chixuzoe@163.com
  • Received Date: 2017-08-10
    Available Online: 2021-01-19
  • Publish Date: 2017-09-15
    Abstract
  •   Objective  To investigate the effect and mechanism of high-dose sirolimus (rapamycin) upon protecting the hepatic ischemia-reperfusion injury (HIRI) in aged mice.  Methods  Twenty C57BL/6 aged mice were randomly and evenly divided into the ischemia-reperfusion injury group (IRI group), low-dose rapamycin pretreatment group (rpm group), high-dose rapamycin pretreatment group (RPM group) and control group (Sham group) using the random number table method (5 mice in each group). In the Sham group, abdominal cavity was incised and sutured alone. In the other three groups, aged mouse 70% HIRI models were established. The ischemia time was 60 min. At preoperative 1 h, rapamycin at a dose of 1 mg/kg and 5 mg/kg was administered via intraperitoneal injection in the rpm and RPM groups. At 12 h post-reperfusion, hematoxylin-eosin (HE) staining was performed to observe the histological changes in the mouse liver. Suzuki grading method was adopted to evaluate the pathological score. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), tumor necrosis factor (TNF)-α and interleukin (IL)-10 and the LC3B-Ⅱ protein level in the liver tissues were quantitatively measured and statistically compared among different groups.  Results  HE staining of the liver tissues revealed normal liver tissues in the Sham group, severe liver cellular injury accompanied with a large quantity of inflammatory cellular infiltration in the IRI and rpm groups. Mild sinusoidal congestion and slight inflammatory cellular infiltration were observed in the RPM group. The pathological score was 5 (4-6) in the RPM group, significantly lower than 7 (5-8) and 8 (7-10) in the rpm and IRI groups (Z=-2.554 and -2.731, both P < 0.05). In terms of postoperative liver function parameters, the AST level was (691±207) U/L in the RPM group, significantly lower compared with (2 032±575) U/L and (1 817±777) U/L in the IRI and rpm groups (t=4.90 and 3.13, both P < 0.05). In the RPM group, the ALT level was measured as (996±584) U/L, considerably lower than (2 992±992) U/L and (2 373±687) U/L in the IRI and rpm groups (t=3.86 and 3.41, both P < 0.05). The AST and ALT levels did not significantly differ between the IRI and rpm groups (both P > 0.05). No statistical significance was identified in the TNF-α and IL-10 levels among different groups (all P > 0.05). Western blot analysis revealed that the relative expression level of LC3B-Ⅱ protein in the liver tissue of the RPM group was significantly higher than those in the Sham, IRI and rpm groups (all P < 0.05).  Conclusions  Administration of high-dose rapamycin exerts a protective effect upon HIRI probably through promoting cellular autophagy in aged mice.

     

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    • References(18)
  • [1]
    项和立, 薛武军, 田普训, 等.心脏死亡器官捐献供体器官功能的评估和维护[J].中华泌尿外科杂志, 2014, 35(1): 20-23. DOI: 10.3760/cma.j.issn.1000-6702. 2014.01.005.

    Xiang HL, Xue WJ, Tian PX, et al. Donor evaluation and maintenance of donation after cardiac death[J]. Chin J Urol, 2014, 35(1): 20-23. DOI: 10.3760/cma.j.issn.1000-6702.2014.01.005.
    [2]
    韩俊峰, 高伟, 沈中阳, 等.肝移植中减轻肝脏缺血再灌注损伤的研究进展[J].中华肝胆外科杂志, 2014, 20(7):547-550. DOI:10.3760/cma.j.issn.1007-8118. 2014.07.019.

    Han JF, Gao W, Shen ZY, et al. Recent progress on strategies for alleviating ischemia reperfusion injury in liver transplantation[J]. Chin J Hepatobiliary Surg, 2014, 20(7): 547-550. DOI: 10.3760/cma.j.issn.1007-8118.2014.07.019.
    [3]
    朱蕾, 张丽.百里醌对肝缺血-再灌注损伤的作用研究[J].器官移植, 2016, 7(2): 144-149. DOI: 10.3969/j.issn.1674-7445.2016.02.013.

    Zhu L, Zhang L. Effect of thymoquinone on hepatic ischemic-reperfusion injury[J]. Organ Transplant, 2016, 7(2): 144-149. DOI: 10.3969/j.issn.1674-7445.2016.02.013.
    [4]
    李势辉, 郭宇, 杨扬, 等. 间充质干细胞与肝缺血再灌注损伤[J/CD]. 中华细胞与干细胞杂志(电子版), 2016, 6(3): 191-194. DOI: 10.3877/cma.j.issn.2095-1221.2016.03.010.

    Li SH, Guo Y, Yang Y, et al. Mesenchymal stem cell and liver ischemia-reperfusion injury[J/CD]. Chin J Cell Stem Cell(Electr Edit), 2016, 6(3): 191-194. DOI: 10.3877/cma.j.issn.2095-1221.2016.03.010.
    [5]
    王清卿, 赵鑫, 陈玉超, 等.肝脏缺血再灌注损伤机制及干预的研究进展[J].临床肝胆病杂志, 2016, 32(6): 1225-1229. DOI: 10.3969/j.issn.1001-5256.2016. 06.049.

    Wang QQ, Zhao X, Chen YC, et al. Research advances in mechanisms and intervention of hepatic ischemia-reperfusion injury[J]. J Clin Hepatol, 2016, 32(6): 1225-1229. DOI: 10.3969/j.issn.1001-5256.2016.06.049.
    [6]
    Dutta S, Sengupta P. Men and mice: relating their ages[J]. Life Sci, 2016, 152:244-248. DOI: 10.1016/j.lfs.2015.10.025.
    [7]
    王国强, 刘洪珍, 杨承祥, 等.雷帕霉素对肝脏缺血再灌注大鼠Beclin-1、Lc-3蛋白表达及细胞凋亡的影响[J].中国老年学杂志, 2015, 35(3): 739-740. DOI: 10.3969/j.issn.1005-9202.2015.03.078.

    Wang GQ, Liu HZ, Yang CX, et al. Effects of rapamycin on expression of Beclin-1 and Lc-3 protein and apoptosis in rats with hepatic ischemia-reperfusion[J]. Chin J Gerontol, 2015, 35(3): 739-740. DOI: 10.3969/j.issn.1005-9202.2015.03.078.
    [8]
    陈广顺, 司中洲, 李杰群, 等.雷帕霉素对大鼠肝脏缺血再灌注损伤的保护作用[J].西安交通大学学报(医学版), 2014, 35(1): 85-88. DOI: 10.7652/jdyxb201401019.

    Chen GS, Si ZZ, Li JQ, et al. Protective effect of RAPA on rat liver ischemia-reperfusion injury[J]. J Xi'an Jiaotong Univ (Med Sci), 2014, 35(1): 85-88. DOI: 10.7652/jdyxb201401019.
    [9]
    Levine B, Kroemer G. Autophagy in the pathogenesis of disease[J]. Cell, 2008, 132(1): 27-42. DOI: 10.1016/j.cell.2007.12.018.
    [10]
    Ashford TP, Porter KR. Cytoplasmic components in hepatic cell lysosomes[J]. J Cell Biol, 1962, 12(1): 198-202. doi: 10.1083/jcb.12.1.198
    [11]
    Czaja MJ, Ding WX, Donohue TM Jr, et al. Functions of autophagy in normal and diseased liver[J]. Autophagy, 2013, 9(8): 1131-1158. DOI: 10.4161/auto.25063.
    [12]
    Wang JH, Behrns KE, Leeuwenburgh C, et al. Critical role of autophage in ischemia/reperfusion injury to aged livers[J]. Autophagy, 2012, 8(1): 140-141. DOI: 10.4161/auto.8.1.18391.
    [13]
    Wang JH, Ahn IS, Fischer TD, et al. Autophagy suppresses age-dependent ischemia and reperfusion injury in livers of mice[J]. Gastroenterology, 2011, 141(6): 2188-2199.e6. DOI: 10.1053/j.gastro.2011.08.005.
    [14]
    Rautou PE, Mansouri A, Lebrec D, et al. Autophagy in liver diseases[J]. J Hepatol, 2010, 53(6): 1123-1134. DOI: 10.1016/j.jhep.2010.07.006.
    [15]
    赵坤, 叶小鸣.自噬与肝移植的研究进展[J].器官移植, 2015, 6(3): 206-208. DOI: 10.3969/j.issn.1674-7445.2015. 03.016.

    Zhao K, Ye XM. Advances on the relationship between autophagy and liver tranplantation[J]. Organ Transplant, 2015, 6(3): 206-208. DOI: 10.3969/j.issn.1674-7445.2015.03.016.
    [16]
    何贤辉, 何健, 欧阳东云, 等.细胞自噬与炎症反应相互作用的研究进展[J].暨南大学学报(自然科学与医学版), 2013, 34(2): 125-128. DOI: 10.3969/j.issn.1000-9965.2013.02.001.

    He XH, He J, Ouyang DY, et al. Advances in the interaction of autophagy with inflammatory response[J]. J Jinan Univ(Nat Sci & Med Edit), 2013, 34(2): 125-128. DOI: 10.3969/j.issn.1000-9965.2013.02.001.
    [17]
    孙雅婧, 郭青龙.细胞自噬的研究进展[J].药学与临床研究, 2012, 20(3): 236-239. DOI: 10.3969/j.issn.1673-7806. 2012.03.015.

    Sun YQ, Guo QL. Research progress of autophagy[J]. Pharm Clin Res, 2012, 20(3): 236-239. DOI: 10.3969/j.issn.1673-7806.2012.03.015.
    [18]
    杨璟辉, 高晓刚, 傅志仁, 等.自噬在肝脏免疫耐受中的作用机制研究进展[J].解放军医学杂志, 2014, 39(6): 503-506. DOI: 10.11855/j.issn.0577-7402.2014. 06.16.

    Yang JH, Gao XG, Fu ZR, et al. Role of autophagy in the mechanism of liver immune tolerance[J]. Med J Chin PLA, 2014, 39(6): 503-506. DOI: 10.11855/j.issn.0577-7402.2014.06.16.
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