异甘草酸镁对刀豆蛋白A诱导的急性肝衰竭小鼠模型的影响

高钰迪; 田原; 张向颖; 张晓慧; 段钟平; 任锋; 陈煜

doi:10.3969/j.issn.1001-5256.2020.07.024

异甘草酸镁对刀豆蛋白A诱导的急性肝衰竭小鼠模型的影响

DOI: 10.3969/j.issn.1001-5256.2020.07.024

1. 首都医科大学附属北京佑安医院疑难肝病及人工肝中心肝衰竭与人工肝治疗研究北京市重点实验室
2. 首都医科大学附属北京佑安医院北京市肝病研究所

基金项目:

国家自然科学基金项目(81770611)；中国肝炎防治基金会天晴肝病基金(TQGB20180213)；国家重点研发计划资助(2017YFA0103000)；北京市医院管理局“登峰”人才培养计划基金资助项目(DFL20151601);北京市医院管理局临床医学发展专项经费资助(ZYLX201806)；国家科技重大专项“艾滋病和病毒性肝炎等重大传染病防治”(2017YFA0103000)；

详细信息

中图分类号: R575.3;R-332
计量
- 文章访问数: 1567
- HTML全文浏览量: 74
- PDF下载量: 216
- 被引次数: 0
出版历程
- 出版日期: 2020-07-20

Effect of magnesium isoglycyrrhizinate on concanavalin A-induced acute liver failure in mice

a. Intractable Hepatic Diseases and Artificial Liver Treatment & Training Center & Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, b. Beijing Hepatology Institute, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China

Research funding:

摘要

摘要:
目的研究异甘草酸镁（Mg IG）对刀豆蛋白A（Con A）诱导的急性肝衰竭小鼠模型的作用及机制。方法选取健康BALB/C小鼠90只,随机分为4组,分别为对照组、Mg IG对照组,每组各10只; Con A模型组、Mg IG+Con A预处理组,每组各35只（其中15只用来计算总生存率）。提取小鼠肝脏及外周血,测定生存率、血清转氨酶水平,肝组织HE染色评价小鼠肝损伤程度,TUNEL荧光染色及caspase-3蛋白活性检测评价小鼠肝细胞凋亡水平,液相芯片法检测小鼠血清炎症细胞因子IL-1β和TNFα含量。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 Con A模型组小鼠总生存率为40%,Mg IG+Con A预处理组小鼠总生存率为80%。Con A模型组血清ALT与AST水平较对照组均显著上升（P值均<0. 01）,Mg IG+Con A预处理组血清ALT与AST水平较Con A模型组均显著降低（P值均<0. 01）。对照组、Mg IG对照组、Con A模型组及Mg IG+Con A预处理组病理评分分别为1. 0±0. 2、1. 2±0. 3、3...
- 肝功能衰竭,急性 /
- 甘草酸 /
- 小鼠,近交BALB C
Abstract:
Objective To investigate the effect of magnesium isoglycyrrhizinate(MgIG) on concanavalin A(ConA)-induced acute liver failure in mice and its mechanism. Methods A total of 60 healthy BALB/C mice were randomly divided into control group with 10 mice,MgIG control group with 10 mice,ConA model group with 20 mice,and MgIG-ConA pretreatment group with 20 mice. The liver and peripheral blood were collected to evaluate survival rate,serum levels of aminotransferases,and degree of liver injury by HE staining of liver tissue; TUNEL fluorescence staining and activity of caspase-3 protein were used to evaluate the apoptosis of hepatocytes; the liquid chip method was used to measure the serum levels of the inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor α(TNFα).A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups. Results The overall survival rate of mice was 40% in the ConA model group and80% in the MgIG-ConA pretreatment group. The ConA model group had significantly increased serum levels of alanine aminotransferase( ALT) and aspartate aminotransferase( AST) compared with the control group( both P < 0. 01),while the MgIG + ConA pretreatment group had significantly reduced serum levels of ALT and AST compared with the ConA model group( both P < 0. 01). The control group,the MgIG control group,the ConA model group,and the MgIG-ConA pretreatment group had a pathological score of 1. 0 ± 0. 2,1. 2 ± 0. 3,3. 7 ±0. 6,and 2. 3 ± 0. 5,respectively,and there was a significant difference between groups( F = 2. 7,P < 0. 05); the apoptotic cells/100 cells ratio was 0. 2 ± 0. 1,0. 1 ± 0. 1,7. 8 ± 1. 3,and 2. 2 ± 0. 4,respectively,in these four groups,and there was a significant difference between groups( F = 27. 6,P < 0. 001); the activity of caspase-3 protein was 0. 813 ± 0. 022,0. 930 ± 0. 033,1. 347 ± 0. 042,and1. 060 ± 0. 053,respectively,in these four groups,and there was a significant difference between groups( F = 51. 072,P < 0. 001).Compared with the control group,the Con A model group had significant increases in serum levels of IL-1β and TNFα( both P < 0. 05);compared with the Con A model group,the Mg IG + Con A pretreatment group had significant reductions in serum levels of IL-1β and TNFα( both P < 0. 05). Conclusion Mg IG exerts a marked protective effect against Con A-induced acute liver failure in mice and can alleviate liver injury possibly by reducing hepatocyte apoptosis and alleviating liver inflammatory response caused by IL-1β and TNFα.
- liver failure,acute /
- glycyrrhizic acid /
- mice,inbred BALB C

HTML全文

参考文献(16)

[1] Liver Failure and Artificial Liver Group,Chinese Society of Infectious Diseases,Chinese Medical Association;Severe Liver Disease and Artificial Liver Group,Chinese Society of Hepatology,Chinese Medical Association.Guideline for diagnosis and treatment of liver failure(2018)[J].J Clin Hepatol,2019,35(1):38-44.(in Chinese)中华医学会感染病学分会肝衰竭与人工肝学组，中华医学会肝病学分会重型肝病与人工肝学组．肝衰竭诊治指南(2018年版)[J]．临床肝胆病杂志，2019,35(1):38-44．

[2]ZHANG YZ,WU XC,LIU YX,et al.Protective effect of silymarin on immunological liver injury induced by concanavalin A in mice[J].Chin J New Drugs Clin Rem,2017,36(7):417-420.(in Chinese)张永州，吴先闯，刘瑜新，等．水飞蓟素对伴刀豆球蛋白A致免疫性肝损伤小鼠的保护作用[J]．中国新药与临床杂志，2017,36(7):417-420．

[3]SONG JW,XING R.Pharmacological effects and clinical applications of magnesium isoglycyrrhizinate[J].China J New Drugs Clin Rem,2012,31(10):578-582,626.(in Chinese)宋佳伟，邢蓉．异甘草酸镁的药理与临床[J]．中国新药与临床杂志，2012,31(10):578-582,626．

[4] MAO HY,TENG HA,LIAO LY,et al.Efficacy of magnesium isoglycyrrhizinate in treatment of severe hepatitis patients with liver failure:A meta-analysis[J/CD].Chin J Liver Dis(Electronic Version),2017,9(1):15-19.(in Chinese)毛海鹰，滕华安，廖礼艳，等．异甘草酸镁治疗重型肝炎肝衰竭疗效的Meta分析[J/CD]．中国肝脏病杂志(电子版)，2017,9(1):15-19．

[5]Chinese Society of Hepatology,Chinese Medical Association.Chinese guidelines on the management of liver cirrhosis[J].J Clin Hepatol,2019,35(11):2408-2425.(in Chinese)中华医学会肝病学分会．肝硬化诊治指南[J]．临床肝胆病杂志，2019,35(11):2408-2425．

[6]ZHAO XJ,YANG YZ,ZHENG YJ,et al.Magnesium isoglycyrrhizinate blocks fructose-induced hepatic NF-κB/NLRP3 inflammasome activation and lipid metabolism disorder[J].Eur J Pharmacol,2017,809:141-150．

[7] ZHENG J,WU G,HU GX,et al.Protective effects against and potential mechanisms underlying the effect of magnesium isoglycyrrhizinate in hypoxia-reoxygenation injury in rat liver cells[J].Genet Mol Res,2015,14(4):15453-15461．

[8] BIAN M,CHEN X,ZHANG C,et al.Magnesium isoglycyrrhizinate promotes the activated hepatic stellate cells apoptosis via endoplasmic reticulum stress and ameliorates fibrogenesis in vitro and in vivo[J].Biofactors,2017,43(6):836-846．

[9] WEN Z,LEI Z,YAO L,et al.Circulating histones are major mediators of systemic inflammation and cellular injury in patients with acute liver failure[J].Cell Death Dis,2016,7(9):e2391．

[10] LI S,XIA Y,CHEN K,et al.Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3[J].Drug Des Devel Ther,2016,10:631-647．

[11] YANG Q,WANG J,LIU R,et al.Amelioration of concanavalin A-induced autoimmune hepatitis by magnesium isoglycyrrhizinate through inhibition of CD4(+)CD25(-)CD69(+)subset proliferation[J].Drug Des Devel Ther,2016,10:443-453．

[12]YU HJ,SHENG GG.Tolerance of concanavalin A in three different strains of mice with acute hepatic injury[J].J Prac Hepatol,2014,17(2):168-171.(in Chinese)于慧杰，盛国光．三种品系小鼠对伴刀豆球蛋白A所致急性肝损伤的耐受性比较研究[J]．实用肝脏病杂志，2014,17(2):168-171．

[13] LAI YC,CHUANG YC,CHANG CP,et al.Macrophage migration inhibitory factor has a permissive role in concanavalin A-induced cell death of human hepatoma cells through autophagy[J].Cell Death Dis,2015,6:e2008．

[14]WANG W,LI X,XU J.Magnesium isoglycyrrhizinate attenuates D-galactosamine/lipopolysaccharides induced acute liver injury of rat via regulation of the p38-MAPK and NF-κB signaling pathways[J].Immunopharmacol Immunotoxicol,2018,40(3):262-267．

[15]LI L,ZHOU J,LI Q,et al.The inhibition of Hippo/Yap signaling pathway is required for magnesium isoglycyrrhizinate to ameliorate hepatic stellate cell inflammation and activation[J].Biomed Pharmacother,2018,106:83-91．

[16] TAN QY,HU Q,ZHU SN,et al.Licorice root extract and magnesium isoglycyrrhizinate protect against triptolide-induced hepatotoxicity via up-regulation of the Nrf2 pathway[J].Drug Deliv,2018,25(1):1213-1223.

施引文献

资源附件(0)

访问统计