Email Alerts
RSS
Volume 38 Issue 8
Aug.  2022
Turn off MathJax
Article Contents
Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2022  >  38(8): 735-743
Xie CQ,Fan FX,Li PT,et al.Effects and mechanism of diammonium glycyrrhizinate on liver injury in severely scalded rats[J].Chin J Burns Wounds,2022,38(8):735-743.DOI: 10.3760/cma.j.cn501225-20220120-00011.
Citation: Xie CQ,Fan FX,Li PT,et al.Effects and mechanism of diammonium glycyrrhizinate on liver injury in severely scalded rats[J].Chin J Burns Wounds,2022,38(8):735-743.DOI: 10.3760/cma.j.cn501225-20220120-00011.
shu

Effects and mechanism of diammonium glycyrrhizinate on liver injury in severely scalded rats

doi: 10.3760/cma.j.cn501225-20220120-00011
  • 1.

    Department of Burns, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China

  • 2.

    Department of Immunology, School of Basic Medical Sciences of Anhui Medical University, Hefei 230032, China

Funds:

Key Science and Technology Project in Anhui Province of China 1604a0802083

More Information
    Abstract
  •   Objective  To investigate the effects and mechanism of diammonium glycyrrhizinate (DG) on liver injury in severely scalded rats.  Methods  The experimental research method was used. Fifty-four female Sprague-Dawley rats aged 7-9 weeks were divided into sham injury group with simulated injury on the back, and simple scald group and scald+DG group with scald of 30% total body surface area on the back, with 18 rats in each group. Rats in sham injury group were not specially treated after injury, and rats in simple scald group and scald+DG group were rehydrated for antishock. Besides, rats in scald+DG group were injected intraperitoneally with 50 mg/kg DG at post injury hour (PIH) 1, 25, and 49. Rats in the three groups were collected, the serum content of liver function injury related indexes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), total protein, and albumin was measured by automatic biochemical assay analyzer, and serum content of ornithine carbamoyl transferase (OCT) was measured by enzyme-linked immunosorbent assay method at PIH 24, 48, and 72; hepatic histopathological changes at PIH 72 were observed by hematoxylin-eosin staining; the mRNA expressions of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), glucose regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), and protein kinase R-like endoplasmic reticulum kinase (PERK) in liver tissue were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction at PIH 24, 48, and 72. The protein expressions of Bcl-2, Bax, GRP78, PERK, and ATF4 in liver tissue were detected by Western blotting at PIH 72 in sham injury group and PIH 24, 48, and 72 in simple scald group and scald+DG group. The number of samples was 6 in each group at each time point. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, and Bonferroni test.  Results  Compared with that in sham injury group, the serum content of AST, ALT, and LDH was significantly increased (P<0.01), and the serum content of total protein and albumin was significantly decreased (P<0.05 or P<0.01) of rats in simple scald group at all post-injury time points. Compared with those in simple scald group, the serum AST content of rats in scald+DG group at PIH 24 was decreased significantly (P<0.05); the serum AST, ALT, and LDH content of rats in scald+DG group at PIH 48 was decreased significantly (P<0.01), and the serum total protein content was increased significantly (P<0.01); the serum AST, ALT, and LDH content of rats in scald+DG group at PIH 72 was decreased significantly (P<0.01), and the serum total protein and albumin content was increased significantly (P<0.01). At PIH 24, 48, and 72, the serum OCT content of rats in simple scald group was (48.5±3.9), (40.8±2.4), and (38.7±2.0) U/L, which was significantly higher than (15.1±2.5), (15.7±2.6), and (16.4±3.7) U/L in sham injury group (P<0.01), and (39.0±4.5), (31.8±2.0), and (22.1±2.6) U/L in scald+DG group (P<0.05 or P<0.01). At PIH 72, the cells in liver tissue of rats in sham injury group had normal morphology and regular arrangement, with no obvious inflammatory cell infiltration; the cells in liver tissue of rats in simple scald group had disordered arrangement, diffuse steatosis, and moderate inflammatory cell infiltration; the cells in liver tissue of rats in scald+DG group arranged regularly, with scattered steatosis and a small amount of inflammatory cell infiltration. Compared with those in sham injury group, the Bcl-2 mRNA (P<0.05 or P<0.01) and protein expressions of liver tissue were significantly decreased, and the mRNA (P<0.01) and protein expressions of Bax were significantly increased in rats in simple scald group at PIH 24, 48, and 72. Compared with those in simple scald group, the mRNA (P<0.05) and protein expressions of Bax in liver tissue of rats in scald+DG group were decreased significantly at PIH 48; the mRNA (P<0.01) and protein expressions of Bax in liver tissue of rats in scald+DG group were significantly decreased, and the mRNA (P<0.01) and protein expressions of Bcl-2 were significantly increased at PIH 72. Compared with those in sham injury group, the mRNA (P<0.05 or P<0.01) and protein expressions of ATF4, GRP78, and PERK in liver tissue were significantly increased in rats in simple scald group at all post-injury time points. Compared with those in simple scald group, the mRNA (P<0.01) and protein expressions of ATF4 in liver tissue of rats in scald+DG group at PIH 48 were significantly decreased, and the mRNA (P<0.05 or P<0.01) and protein expressions of ATF4, GRP78, and PERK were significantly decreased in liver tissue of rats in scald+DG group at PIH 72.  Conclusions  DG can effectively reduce the degree of liver injury in rats after severe scald, and the mechanism may involve alleviating endoplasmic reticulum stress and mitigating mitochondrial damage.

     

    • FullText(HTML)
  • loading
    • References(32)
  • [1]
    HeylandDK,WischmeyerP,JeschkeMG,et al.A randomized trial of enteral glutamine to minimize thermal injury (the re-energize trial): a clinical trial protocol[J].Scars Burn Heal,2017,3:2059513117745241.DOI: 10.1177/2059513117745241.
    [2]
    GongY,LongX,XuH,et al.The changes and prognostic value of liver function in young adults with severe burn: a retrospective observational study[J].Medicine (Baltimore),2018,97(51):e13721.DOI: 10.1097/MD.0000000000013721.
    [3]
    BrusselaersN,HosteEA,MonstreyS,et al.Outcome and changes over time in survival following severe burns from 1985 to 2004[J].Intensive Care Med,2005,31(12):1648-1653.DOI: 10.1007/s00134-005-2819-6.
    [4]
    AbdullahiA,BarayanD,VinaikR,et al.Activation of ER stress signalling increases mortality after a major trauma[J].J Cell Mol Med,2020,24(17):9764-9773.DOI: 10.1111/jcmm.15548.
    [5]
    王全楚,申德林,刘文德.创伤后应激性肝损伤发病情况调查分析[J].实用医药杂志,2006,23(1):58-59.DOI: 10.3969/j.issn.1671-4008.2006.01.029.
    [6]
    PapadopoulosD,SiempisT,TheodorakouE,et al.Hepatic ischemia and reperfusion injury and trauma: current concepts[J].Arch Trauma Res,2013,2(2):63-70.DOI: 10.5812/atr.12501.
    [7]
    TakE,ParkGC,KimSH,et al.Epigallocatechin-3-gallate protects against hepatic ischaemia-reperfusion injury by reducing oxidative stress and apoptotic cell death[J].J Int Med Res,2016,44(6):1248-1262.DOI: 10.1177/0300060516662735.
    [8]
    廖永晖,千年松,张毅,等.创伤应激与肝细胞凋亡[J].世界华人消化杂志,2010,18(15):1569-1576.DOI: 10.3969/j.issn.1009-3079.2010.15.009.
    [9]
    肖潇,杨平,张燕,等.创伤应激性肝损伤的机制与临床[J].创伤外科杂志,2019,21(11):871-873.DOI: 10.3969/j.issn.1009-4237.2019.11.18.
    [10]
    周萍,黄宏,陈林.烧伤后大鼠肝脏的病理形态学变化与肝功能的关系[J].中国危重病急救医学,2002,14(4):201-203.DOI: 10.3760/j.issn:1003-0603.2002.04.004.
    [11]
    黄跃生.烧伤外科学[M]. 北京:科学技术文献出版社,2010:335-337.
    [12]
    LiP,XiaZ,KongW,et al.Exogenous L-carnitine ameliorates burn-induced cellular and mitochondrial injury of hepatocytes by restoring CPT1 activity[J].Nutr Metab (Lond),2021,18(1):65.DOI: 10.1186/s12986-021-00592-x.
    [13]
    FatimaA,MalickTS,KhanI,et al.Effect of glycyrrhizic acid and 18β-glycyrrhetinic acid on the differentiation of human umbilical cord-mesenchymal stem cells into hepatocytes[J].World J Stem Cells,2021,13(10):1580-1594.DOI: 10.4252/wjsc.v13.i10.1580.
    [14]
    LiJY,CaoHY,LiuP,et al.Glycyrrhizic acid in the treatment of liver diseases: literature review[J].Biomed Res Int,2014,2014:872139.DOI: 10.1155/2014/872139.
    [15]
    El-Saber BatihaG,Magdy BeshbishyA,El-MleehA,et al.Traditional uses, bioactive chemical constituents, and pharmacological and toxicological activities of glycyrrhiza glabra L. (fabaceae)[J].Biomolecules,2020,10(3):352. DOI: 10.3390/biom10030352.
    [16]
    王浩楠,梁士兵,姚晓玲,等.复方甘草酸苷注射液改善慢性乙型肝炎肝损伤疗效和安全性的系统评价与Meta分析[J].中国中药杂志,2021,46(3):694-702.DOI: 10.19540/j.cnki.cjcmm.20200705.501.
    [17]
    余梅香,马小琴,杨婉花.联合使用甘草酸二铵治疗药物性肝损伤的疗效及安全性单中心真实世界研究[J].世界临床药物,2019,40(7):486-492.DOI: 10.13683/j.wph.2019.07.006.
    [18]
    何剑,阳学风.甘草酸二铵肠溶胶囊联合硫普罗宁肠溶片治疗非酒精性脂肪肝的临床研究[J].中国临床药理学杂志,2019,35(9):833-835. DOI: 10.13699/j.cnki.1001-6821.2019.09.003.
    [19]
    张水良.甘草酸二铵对烧伤患者肝功能异常的疗效分析[J].中华急诊医学杂志,2012,21(9):1053-1054. DOI: 10.3760/cma.j.issn.1671-0282.2012.09.034.
    [20]
    金汉宏,郑国平,陈武荣,等.甘草酸二铵对烧伤患者肝功能异常的治疗作用[J].中华烧伤杂志,2005,21(5):353-355.DOI: 10.3760/cma.j.issn.1009-2587.2005.05.011.
    [21]
    JeschkeMG,MicakRP,FinnertyCC,et al.Changes in liver function and size after a severe thermal injury[J].Shock,2007,28(2):172-177.DOI: 10.1097/shk.0b013e318047b9e2.
    [22]
    KaoTC,WuCH,YenGC.Glycyrrhizic acid and 18β-glycyrrhetinic acid recover glucocorticoid resistance via PI3K-induced AP1, CRE and NFAT activation[J].Phytomedicine,2013,20(3/4):295-302.DOI: 10.1016/j.phymed.2012.10.013.
    [23]
    GaoM,LiX,HeL,et al.Diammonium glycyrrhizinate mitigates liver injury via inhibiting proliferation of NKT cells and promoting proliferation of tregs[J].Drug Des Devel Ther,2019,13:3579- 3589.DOI: 10.2147/DDDT.S220030.
    [24]
    WangM,KaufmanRJ.Protein misfolding in the endoplasmic reticulum as a conduit to human disease[J].Nature,2016,529(7586):326-335.DOI: 10.1038/nature17041.
    [25]
    XiangF, MaSY, LvYL, et al. Tumor necrosis factor receptor- associated protein 1 regulates hypoxia-induced apoptosis through a mitochondria-dependent pathway mediated by cytochrome c oxidase subunit II[J/OL]. Burns Trauma, 2019,7:16[2022-01-20]. https://pubmed.ncbi.nlm.nih.gov/31143823/. DOI: 10.1186/s41038-019-0154-3.
    [26]
    ShiM,ChaiY,ZhangJ,et al.Endoplasmic reticulum stress- associated neuronal death and innate immune response in neurological diseases[J].Front Immunol,2022,12:794580.DOI: 10.3389/fimmu.2021.794580.
    [27]
    孔维昌,夏正国,田曦茜,等.早期补充外源性肉碱对严重烫伤大鼠肝脏线粒体损伤的影响及病理机制[J].中华烧伤杂志,2018,34(6):374-379. DOI: 10.3760/cma.j.issn.1009-2587.2018.06.012.
    [28]
    DingeldeinA,PokornáŠ,LidmanM,et al.Apoptotic Bax at oxidatively stressed mitochondrial membranes: lipid dynamics and permeabilization[J].Biophys J,2017,112(10):2147-2158.DOI: 10.1016/j.bpj.2017.04.019.
    [29]
    JiaSZ,XuXW,ZhangZH,et al.Selenoprotein K deficiency- induced apoptosis: a role for calpain and the ERS pathway[J].Redox Biol,2021,47:102154.DOI: 10.1016/j.redox.2021.102154.
    [30]
    褚万立,柴家科,冯永强,等.严重烧伤大鼠肝脏内质网应激相关蛋白的表达及其意义[J].中华医学杂志,2012,92(12):853-856. DOI: 10.3760/cma.j.issn.0376-2491.2012.12.019.
    [31]
    WangH, ShiX, QiuM,et al. Hydrogen sulfide plays an important protective role through influencing endoplasmic reticulum stress in diseases[J]. Int J Biol Sci,2020,16(2):264- 271. DOI: 10.7150/ijbs.38143.
    [32]
    SenftD,RonaiZA.UPR, autophagy, and mitochondria crosstalk underlies the ER stress response[J].Trends Biochem Sci,2015,40(3):141-148.DOI: 10.1016/j.tibs.2015.01.002.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(4)  / Tables(3)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (3384) PDF downloads(16) Cited by()
    Proportional views
    Related

    Copyright © Chinese Journal of Burns京ICP备07035254号-14

    E-mail：shaoshangzazhi@163.com

    Website：https://zhsszz.xml-journal.net/

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return