中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 35 Issue 12
Dec.  2019
Turn off MathJax
Article Contents

Clinical effect of Qingre Jiedu Liangxue prescription in treatment of mice with acute-on-chronic liver failure and related mechanism

DOI: 10.3969/j.issn.1001-5256.2019.12.025
Research funding:

 

  • Received Date: 2019-07-17
  • Published Date: 2019-12-20
  • Objective To investigate the mechanism of action of Qingre Jiedu Liangxue prescription in the treatment of mice with acute-on-chronic liver failure( ACLF). Methods A total of 36 male C57 BL/6 mice were randomly divided into normal group( n = 6),traditional Chinese medicine( TCM) group( n = 6),Western medicine group( n = 6),and model group( n = 18). All mice except those in the normal group were given intraperitoneal injection of 10% CCl4 three times a week for 8 weeks,and LPS 0. 5 mg/kg and D-gal 400 mg/kg were given after last injection. The mice in the model group were sacrificed at 3,12,and 24 hours after D-gal administration. After 4 weeks of intraperitoneal injection of 10% CCl4,the mice in the TCM group and the Western medicine group were given TCM or Western medicine by gavage for 4 weeks and were sacrificed at 3 hours after D-gal administration. Serum levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),and inflammatory factors were measured; HE staining and picrosirius red staining were used to observe liver pathological changes; immunofluorescence assay was used to observe F4/80 and CD11 b; immunohistochemistry was used to measure the expression of myeloperoxidase( MPO); Western blot was used to measure the expression of CD44,intercellular adhesion molecule-1( ICAM-1),and high-mobility group box 1( HMGB1). A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the SNK-q test was used for further comparison between two groups. Results Compared with the normal group,the 3-hour model group had significant increases in the serum levels of ALT and AST χ2= 51. 41 and 71. 22,( both P < 0. 001),and comparedwith the 3-hour model group,the TCM group had a significant increase in the serum level of interleukin-17 A( IL-17 A) and significant reductions in tumor necrosis factor-α( TNFα),granulocyte-macrophage colony-stimulating factor( GM-CSF),and interleukin-10( IL-10)( all P < 0. 01),as well as significant reductions in the expression of interleukin-1β( IL-1β),monocyte chemotactic protein 1( MCP-1),and interferon gamma( IFNγ)( all P < 0. 05). Compared with the model group,the Western medicine group had significant reductions in the serum levels of GM-CSF,IFNγ,and interferon beta( all P < 0. 05). HE staining showed that compared with the normal group,the model group had severe hepatocyte injury and significant inflammatory cell infiltration. Liver pathological changes were improved after the administration of TCM and Western medicine. The 3-hour model group had a significant increase in the expression of MPO compared with the normal group( P < 0. 05),and the expression of MPO gradually decreased in the 12-and 24-hour model groups( P<0. 05); the TCM group had a significant reduction in the expression of MPO compared with the 3-hour model group( P < 0. 05). The model group had significant increases in the expression of F4/80 and CD11 b compared with the normal group,and the TCM group had significant increases in the expression of F4/80 and CD11 b compared with the 3-hour model group. The model group had significant increases in the expression of CD44 and ICAM-1 compared with the normal group( both P < 0. 05),and the TCM and Western medicine groups had significant reductions in the expression of HMGB1,CD44,and ICAM-1 compared with the 3-hour model group( all P < 0. 05). Conclusion In mice with ACLF,Qingre Jiedu Liangxue prescription can reduce the serum levels of ALT and AST,improve liver injury,increase IL-17 A,and reduce TNFα,GM-CSF,IL-10,IL-1β,MCP-1,and IFNγ. In addition,Qingre Jiedu Liangxue prescription can reduce the expression of MPO,CD44,ICAM-1,and HMGB1 and increase the expression of F4/80 and CD11 b in liver tissue. It is suggested that Qingre Jiedu Liangxue prescription can improve liver injury by regulating neutrophils and Kupffer cells,and further studies are needed to investigate the specific mechanism.

     

  • loading
  • [1] SARA BA. Acute-on-chronic liver failure:Pathogenesis,prognostic factors and management[J]. World J Gastroenterol,2015,21(42):12125-12140.
    [2] LUO L,ZHANG QF,ZHANG DZ. Advances in the treatment of acute liver failure[J]. J Clin Hepatol,2018,34(2):438-443.(in Chinese)骆玲,张琼方,张大志.急性肝衰竭的治疗进展[J].临床肝胆病杂志,2018,34(2):438-443.
    [3] LIU HM,GAO FY,JIANG YY,et al. Clinical observation on 30cases of hepatitis B at early stage of acute-on-chronic liver failure treated by Modified Jiedu Liangxue Lishi Fang combined with western medicine[J]. J Tradit Chin Med,2018,59(1):41-45.(in Chinese)刘慧敏,高方媛,江宇泳,王宪波.解毒凉血利湿方加减联合西药治疗乙型肝炎慢加急性肝衰竭前期30例临床观察[J].中医杂志,2018,59(1):41-45.
    [4] WANG XB,WANG XJ. Guidelines for clinical diagnosis and treatment of acute-on-chronic liver failure in traditional Chinese medicine[J]. J Clin Hepatol,2019,35(3):494-503.(in Chinese)王宪波,王晓静.慢加急性肝衰竭中医临床诊疗指南[J].临床肝胆病杂志,2019,35(3):494-503.
    [5] NI S,LI S,YANG N,et al. Deregulation of regulatory T cells in acute-on-chronic liver failure:A rat model[J]. Mediators Inflamm,2017,2017:1390458.
    [6] ZHANG YJ. Clinical observation on Qingchang Jiedu Recipe for the treatment of endotoxemia with acute-on-chronic liver failure[J]. J Emerg Tradit Chin Med,2015,24(7):1264-1265.(in Chinese)张育菁.自拟清肠解毒方灌肠辅助治疗慢加急性肝衰竭内毒素血症的临床观察[J].中国中医急症,2015,24(7):1264-1265.
    [7] DENG QZ,XIA BE,WANG SH,et al. Study on the effects of smilax glabra rhizome composition on patients with hepatitis B combined with acute-on-chronic hepatic failure[J]. China J Tradit Chin Med Pharma,2015,30(3):739-742.(in Chinese)邓勤智,夏邦恩,王世和,等.土茯苓组方在乙型肝炎病毒慢加急性肝衰竭中的应用及疗效分析[J].中华中医药杂志,2015,30(3):739-742.
    [8] ZHAO BL. Research on clinical evaluation and mechanism for treating acute-on-chronic hepatitis B liver failure by the Jiedu Liangxue therapy[J]. Clin J Chin Med,2015,7(32):59-60.(in Chinese)赵宝利.解毒凉血法治疗乙型肝炎慢加急性肝衰竭的疗效评价及机制研究[J].中医临床研究,2015,7(32):59-60.
    [9] PANG GH,YANG RL. Traditional Chinese medicine and western medicine in the treatment of chronic hepatitis B patients with acute liver failure[J]. Jilin J Tradit Chin Med,2017,37(4):363-366.(in Chinese)庞国宏,杨汝磊.中西医辨证治疗乙型肝炎病毒慢加急性肝衰竭[J].吉林中医药,2017,37(4):363-366.
    [10] XU R,HUANG H,ZHANG Z,et al. The role of neutrophils in the development of liver diseases[J]. Cell Mol Immunol,2014,11(3):224-231.
    [11] WANG L,LI LP,XING X,et al. Hepatic macrophages in liver injury and repair[J]. Chin J Clin Pharmacol Ther,2018,23(10):1188-1195.(in Chinese)王鹿,李丽萍,邢欣,等.肝脏巨噬细胞及其在肝损伤和修复中的作用[J].中国临床药理学与治疗学,2018,23(10):1188-1195.
    [12] LIAO YH,XIA N,ZHOU SF,et al. Interleukin-17A contributes to myocardial ischemia/reperfusion injury by regulating cardiomyocyte apoptosis and neutrophil infiltration[J]. J Am Coll Cardiol,2012,59(4):420-429.
    [13] ANDERSSON U,TRACEY KJ. HMGB1 is a therapeutic target for sterile inflammation and infection[J]. Annu Rev Immunol,2011,29(1):139-162.
    [14] OSHIMA G,SHINODA M,TANABE M,et al. Increased plasma levels of high mobility group box 1 in patients with acute liver failure[J]. Eur Surg Res,2012,48(3):154-162.
    [15] DUAN XZ,HU JH,LI C,et al. Relation between serum levels of high mobility group box 1 and hepatitis B virus-related acute-on-chronic liver failure[J]. Chin J Hepatol,2013,21(6):434-437.(in Chinese)段学章,胡瑾华,李晨,等.血清高迁移率族蛋白1在乙型肝炎病毒相关慢加急性肝衰竭患者中的特点及其临床意义[J].中华肝脏病杂志,2013,21(6):434-437.
    [16] SAPPINGTON PL,YANG R,YANG H,et al. HMGB1 B box increases the permeability of Caco-2 enterocytic monolayers and impairs intestinal barrier function in mice[J]. Gastroenterology,2002,123(3):790-802.
    [17] YANG H,HREGGVIDSDOTTIR HS,PALMBLAD K,et al. A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release[J].Proc Natl Acad Sci U S A,2010,107(26):11942-11947.
  • 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

    Article Metrics

    Article views (1186) PDF downloads(234) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return