中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

线粒体靶向抗氧化剂SS-31对脓毒症小鼠模型急性肝损伤的影响

满明银 李娜娜 卜月 于凯江

引用本文:
Citation:

线粒体靶向抗氧化剂SS-31对脓毒症小鼠模型急性肝损伤的影响

DOI: 10.3969/j.issn.1001-5256.2022.02.025
基金项目: 

国家自然科学基金 (81770276)

利益冲突声明:本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突,特此声明。
作者贡献声明:满明银负责课题设计,资料分析,撰写论文;李娜娜参与收集数据,修改论文;卜月负责实验及修改论文;于凯江负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    于凯江,drkaijiang@163.com

Influence of mitochondria-targeted antioxidant SS-31 on acute liver injury in a mouse model of sepsis

Research funding: 

National Natural Science Foundation of China (81770276)

More Information
  • 摘要:   目的  探究线粒体靶向抗氧化剂SS-31对脓毒症小鼠模型急性肝损伤的作用。  方法  将24只C57BL/6J成年雄性小鼠随机分为control组、control+SS-31组、脂多糖(LPS)组(脓毒症组)、LPS+SS-31组,每组6只。小鼠腹腔注射LPS(10 mg/kg)制备脓毒症急性肝损伤模型或对照组腹腔注射等体积PBS液,继之腹腔注射SS-31(10 mg/kg)进行治疗或对照组腹腔注射等体积生理盐水,12 h后ELISA法检测ALT、AST、活性氧(ROS)、超氧化物歧化酶(SOD)、TNFα、IL-1β、IL-6水平,HE染色观察肝脏组织病理学。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。  结果  与LPS组相比,LPS+SS-31组小鼠血清中ALT[(140.05±12.22) U/L vs (102.64±8.75)U/L]、AST[(80.22±4.71)U/L vs (69.26±5.37)U/L],以及肝组织中ROS[(1 030.21±115.87) pg/mL vs (847.84±63.65) pg/mL]、TNFα[(767.18±60.60) ng/mL vs (698.89±16.99) ng/mL]、IL-1β[(29.97±1.37) ng/mL vs (26.70±3.09) ng/mL]、IL-6[(59.13±7.09) pg/mL vs (49.29±3.41) pg/mL)]均显著降低(P值均<0.05);与control组比较,LPS组小鼠肝组织切片HE染色显示出肝小叶结构破坏、炎性细胞浸润、细胞间隙模糊、肝细胞肿胀; LPS+SS-31组炎性细胞浸润减少,肝细胞肿胀减轻。  结论  线粒体靶向抗氧化剂SS-31可降低ROS水平,下调脓毒症时高表达的炎性因子,减轻小鼠脓毒症相关急性肝损伤。

     

  • 图  1  肝组织病理切片(HE染色,×400)

    注:a,control组;b,control+SS-31组;c,LPS组;d,LPS+SS-31组。

    表  1  4组小鼠各指标比较

    项目 control组
    (n=6)
    control+SS-31组
    (n=6)
    LPS组
    (n=6)
    LPS+SS-31组
    (n=6)
    F P
    体质量(g) 20.83±1.68 21.03±1.35 21.53±1.36 20.93±1.37 0.275 0.843
    血清指标
      ALT(U/L) 73.76±4.72 74.67±8.88 140.05±12.221) 102.64±8.752)3) 71.428 <0.001
      AST(U/L) 50.66±1.99 48.75±4.28 80.22±4.711) 69.26±5.372)3) 75.073 <0.001
    氧化应激指标
      ROS(pg/mL) 704.13±60.08 660.39±84.44 1 030.21±115.871) 847.84±63.652)3) 23.679 <0.001
      SOD(pg/mL) 761.84±36.36 736.56±31.15 638.72±22.201) 615.00±46.222) 25.305 <0.001
    炎性指标
      TNFα(ng/mL) 618.69±56.28 618.95±59.52 767.18±60.601) 698.89±16.992)3) 11.526 <0.001
      IL-1β(ng/mL) 23.34±1.05 23.24±0.96 29.97±1.371) 26.70±3.092)3) 18.253 0.001
      IL-6(pg/mL) 43.19±7.79 42.96±5.56 59.13±7.091) 49.29±3.412)3) 8.985 0.001
    注:与control组比较,1)P<0.05;与control+SS-31组比较,2)P<0.05;与LPS组比较,3)P<0.05。
    下载: 导出CSV
  • [1] SINGER M, DEUTSCHMAN CS, SEYMOUR CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3)[J]. JAMA, 2016, 315(8): 801-810. DOI: 10.1001/jama.2016.0287.
    [2] FLEISCHMANN C, SCHERAG A, ADHIKARI NK, et al. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations[J]. Am J Respir Crit Care Med, 2016, 193(3): 259-272. DOI: 10.1164/rccm.201504-0781OC.
    [3] WANG L, QIU YL, WANG JS. Advances in research and application of liver organoids[J]. J Clin Hepatol, 2019, 35(10): 2342-2345. DOI: 10.3969/j.issn.1001-5256.2019.10.047.

    王利, 丘倚灵, 王建设. 肝类器官研究及应用进展[J]. 临床肝胆病杂志, 2019, 35(10): 2342-2345. DOI: 10.3969/j.issn.1001-5256.2019.10.047.
    [4] WANG DD, SONG J, ZHANG XL. Research advances in the role of gut microbiota in liver diseases[J]. J Clin Hepatol, 2019, 35(9): 2120-2123. DOI: 10.3969/j.issn.1001-5256.2019.09.053.

    王丹丹, 宋佳, 张晓岚. 肠道菌群在肝脏疾病中的作用[J]. 临床肝胆病杂志, 2019, 35(9): 2120-2123. DOI: 10.3969/j.issn.1001-5256.2019.09.053.
    [5] XING BM, GUO N, NING HH, et al. Sepsis liver damage and autophagy[J/CD]. Chin J Liver Dis (Electronic Version), 2021, 13(3): 37-41. DOI: 10.3969/j.issn.1674-7380.2021.03.006.

    邢博民, 郭娜, 宁海慧, 等. 脓毒症肝损伤与自噬[J/CD]. 中国肝脏病杂志(电子版), 2021, 13(3): 37-41. DOI: 10.3969/j.issn.1674-7380.2021.03.006.
    [6] KOBASHI H, TOSHIMORI J, YAMAMOTO K. Sepsis-associated liver injury: Incidence, classification and the clinical significance[J]. Hepatol Res, 2013, 43(3): 255-266. DOI: 10.1111/j.1872-034X.2012.01069.x.
    [7] MARSHALL JC. New translational research provides insights into liver dysfunction in sepsis[J]. PLoS Med, 2012, 9(11): e1001341. DOI: 10.1371/journal.pmed.1001341.
    [8] FUCHS M, SANYAL AJ. Sepsis and cholestasis[J]. Clin Liver Dis, 2008, 12(1): 151-172, ix. DOI: 10.1016/j.cld.2007.11.002.
    [9] CHIAO YA, ZHANG H, SWEETWYNE M, et al. Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice[J]. Elife, 2020, 9: e55513. DOI: 10.7554/eLife.55513.
    [10] YANG L, ZHAO K, CALINGASAN NY, et al. Mitochondria targeted peptides protect against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine neurotoxicity[J]. Antioxid Redox Signal, 2009, 11(9): 2095-2104. DOI: 10.1089/ars.2009.2445.
    [11] TALBERT EE, SMUDER AJ, MIN K, et al. Immobilization-induced activation of key proteolytic systems in skeletal muscles is prevented by a mitochondria-targeted antioxidant[J]. J Appl Physiol (1985), 2013, 115(4): 529-538. DOI: 10.1152/japplphysiol.00471.2013.
    [12] SZETO HH, LIU S, SOONG Y, et al. Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury[J]. J Am Soc Nephrol, 2011, 22(6): 1041-1052. DOI: 10.1681/ASN.2010080808.
    [13] WU J, HAO S, SUN XR, et al. Elamipretide (SS-31) ameliorates isoflurane-induced long-term impairments of mitochondrial morphogenesis and cognition in developing rats[J]. Front Cell Neurosci, 2017, 11: 119. DOI: 10.3389/fncel.2017.00119.
    [14] ALLEN ME, PENNINGTON ER, PERRY JB, et al. The cardiolipin-binding peptide elamipretide mitigates fragmentation of cristae networks following cardiac ischemia reperfusion in rats[J]. Commun Biol, 2020, 3(1): 389. DOI: 10.1038/s42003-020-1101-3.
    [15] ZHANG XT, LIU JZ, LI P, et al. Research progress of mitophagy in sepsis[J]. China Med Herald, 2021, 18(10): 39-42. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202110011.htm

    张欣桐, 刘景卓, 李盼, 等. 线粒体自噬在脓毒症中的研究进展[J]. 中国医药导报, 2021, 18(10): 39-42. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202110011.htm
    [16] SUN XD, YAN YH, ZHANG YT, et al. Effects of Xuebijing injection on oxidative stress and early inflammatory factors in rats with sepsis induced liver injury[J]. Chin J Mod Appl Pharm, 2016, 33(10): 1255-1259. DOI: 10.13748/j.cnki.issn1007-7693.2016.10.008.

    孙雪东, 严一核, 张亦婷, 等. 血必净对脓毒症肝损伤大鼠氧化应激及炎症状态的影响[J]. 中国现代应用药学, 2016, 33(10): 1255-1259. DOI: 10.13748/j.cnki.issn1007-7693.2016.10.008.
    [17] ZHAO W, XU Z, CAO J, et al. Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice[J]. J Neuroinflammation, 2019, 16(1): 230. DOI: 10.1186/s12974-019-1627-9.
    [18] SMUDER AJ, ROBERTS BM, WIGGS MP, et al. Pharmacological targeting of mitochondrial function and reactive oxygen species production prevents colon 26 cancer-induced cardiorespiratory muscle weakness[J]. Oncotarget, 2020, 11(38): 3502-3514. DOI: 10.18632/oncotarget.27748.
    [19] HAO ZH, HUANG Y, WANG MR, et al. SS31 ameliorates age-related activation of NF-κB signaling in senile mice model, SAMP8[J]. Oncotarget, 2017, 8(2): 1983-1992. DOI: 10.18632/oncotarget.14077.
    [20] BUTLER J, KHAN MS, ANKER SD, et al. Effects of elamipretide on left ventricular function in patients with heart failure with reduced ejection fraction: The PROGRESS-HF phase 2 trial[J]. J Card Fail, 2020, 26(5): 429-437. DOI: 10.1016/j.cardfail.2020.02.001.
    [21] KARAA A, HAAS R, GOLDSTEIN A, et al. Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy[J]. Neurology, 2018, 90(14): e1212-e1221. DOI: 10.1212/WNL.0000000000005255.
  • 加载中
图(1) / 表(1)
计量
  • 文章访问数:  592
  • HTML全文浏览量:  197
  • PDF下载量:  45
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-06-10
  • 录用日期:  2021-08-26
  • 出版日期:  2022-02-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回