Surgery Today

, Volume 41, Issue 8, pp 1075–1084 | Cite as

Matrine attenuates endotoxin-induced acute liver injury after hepatic ischemia/reperfusion in rats

  • Feng Zhang
  • Xun Wang
  • Liquan Tong
  • Haiquan Qiao
  • Xinlei Li
  • Liguang You
  • Hongchi Jiang
  • Xueying Sun
Original Article



Hepatic ischemia/reperfusion (HIR) injury is an unavoidable consequence of major liver surgery, during which endotoxemia often takes place. This study aimed to investigate whether matrine has a protective effect against HIR-induced liver injury aggravated by endotoxin.


Wistar rats were subjected to 30 min of HIR followed by lipopolysaccharide (LPS) (0.5 mg/kg) administration. At the indicated time points, six rats from each group (24 rats) were randomly euthanized to collect blood samples and livers.


Preadministration of matrine protected livers from injury induced by HIR+LPS as the histological score, myeloperoxidase activity and malondialdehyde contents, expression of macrophage-inflammatory protein-2, DNA-binding activity of nuclear factor κB, and serum levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, tumor necrosis factor-α, soluble intercellular adhesion molecule-1, and nitric oxide were significantly reduced, and serum levels of interleukin-6 were further increased. HIR+LPS markedly induced cell apoptosis and necrosis, and upregulated the expression of cleaved caspase-3, Fas, and FasL. Matrine significantly reduced cell necrosis, but had a nonsignificant inhibitory effect on cell apoptosis and expression of cleaved caspase-3 and FasL


Matrine attenuates endotoxin-induced acute liver injury after HIR mainly by its anti-inflammatory and antioxidative activities, and has little inhibitory effect on cell apoptosis.

Key words

Matrine Endotoxemia Hepatic ischemia/reperfusion Inflammatory cytokine Oxidative stress Apoptosis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Selzner M, Rudiger HA, Sindram D, Madden J, Clavien PA. Mechanisms of ischemic injury are different in the steatotic and normal rat liver. Hepatology 2000;32:1280–1288.PubMedCrossRefGoogle Scholar
  2. 2.
    Xing HC, Li LJ, Xu KJ, Shen T, Chen YB, Chen Y, et al. Effects of Salvia miltiorrhiza on intestinal microflora in rats with ischemia reperfusion liver injury. Hepatobiliary Pancreat Dis Int 2005;4:274–280.PubMedGoogle Scholar
  3. 3.
    Watanabe M, Chijiiwa K, Kameoka N, Yamaguchi K, Kuroki S, Tanaka M. Gadolinium pre-treatment decreases survival and impair liver regeneration after partial hepatectomy under ischemia reperfusion in rats. Surgery 2000;127:456–463.PubMedCrossRefGoogle Scholar
  4. 4.
    Kono H, Fujii H, Matsuda M, Yamamoto M, Matsumoto Y. Gadolinium chloride prevents mortality in hepatectomized rats given endotoxin. J Surg Res 2001;96:204–210.PubMedCrossRefGoogle Scholar
  5. 5.
    Suzuki S, Nakamura S, Serizawa A, Sakaguchi T, Konno H, Muro H. Role of Kupffer cells and the spleen in modulation of endotoxin-induced liver injury after partial hepatectomy. Hepatology 1996;24:219–225.PubMedCrossRefGoogle Scholar
  6. 6.
    Seki S, Habu Y, Kawamura T, Takeda K, Dobashi H, Ohkawa T, et al. The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper immune responses. Immuno Rev 2000;174:35–46.CrossRefGoogle Scholar
  7. 7.
    Deutschman CS, Haber BA, Andrejko K, Cressman DE, Harrison R, Elenko E, et al. Increased expression of cytokine-induced neutrophil chemoattractant in septic rat liver. Am J Physiol 1996;271:R593–R600.PubMedGoogle Scholar
  8. 8.
    Bellezzo JM, Britton RS, Bacon BR, Fox ES. LPS-mediated NFkappa beta activation in rat Kupffer cells can be induced independently of CD14. Am J Physiol 1996;270:G956–G961.PubMedGoogle Scholar
  9. 9.
    Fernandez ED, Flohe S, Siemers F, Nau M, Ackermann M, Ruwe M, et al. Endotoxin tolerance protects against local hepatic ischemia reperfusion injury in the rat. J Endotoxin Res 2000;6:321–328.PubMedCrossRefGoogle Scholar
  10. 10.
    Li Y, Wang B, Zhou C, Bi Y. Matrine induces apoptosis in angiotensin II-stimulated hyperplasia of cardiac fibroblasts: effects on Bcl-2/Bax expression and caspase-3 activation. Basic Clin Pharmacol Toxicol 2007;101:1–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Liu J, Zhu M, Shi R, Yang M. Radix Sophorae flavescentis for chronic hepatitis B: a systematic review of randomized trials. Am J Chin Med 2003;31:337–354.PubMedCrossRefGoogle Scholar
  12. 12.
    Long Y, Lin XT, Zeng KL, Zhang L. Efficacy of intramuscular matrine in the treatment of chronic hepatitis B. Hepatobiliary Pancreat Dis Int 2004;3:69–72.PubMedGoogle Scholar
  13. 13.
    Zhang JP, Zhang M, Jin C, Zhou B, Xie WF, Guo C, et al. Matrine inhibits production and actions of fibrogenic cytokines released by mouse peritoneal macrophages. Acta Pharmacol Sin 2001;22:765–768.PubMedGoogle Scholar
  14. 14.
    Suo Z, Liu Y, Ferreri M, Zhang T, Liu Z, Mu X, et al. Impact of matrine on inflammation related factors in rat intestinal microvascular endothelial cells. J Ethnopharmacol 2009;125:404–409.PubMedCrossRefGoogle Scholar
  15. 15.
    Zhao Y, Zhai D, He H, Liu J, Li T, Chen X, et al. Matrine improves 17alpha-ethinyl estradiol-induced acute cholestasis in rats. Hepatol Res 2009;39:1144–1149.PubMedCrossRefGoogle Scholar
  16. 16.
    Wan XY, Luo M, Li XD, He P. Hepatoprotective and antihepatocarcinogenic effects of glycyrrhizin and matrine. Chem Biol Interact 2009;181:15–19.PubMedCrossRefGoogle Scholar
  17. 17.
    Xu X, Ling Q, Gao F, He ZL, Xie HY, Zheng SS. Hepatoprotective effects of marine and kuhuang in liver transplant recipients. Am J Chin Med 2009;37:27–34.PubMedCrossRefGoogle Scholar
  18. 18.
    Park SJ, Nam KW, Lee HJ, Cho EY, Koo U, Mar W. Neuroprotective effects of an alkaloid-free ethyl acetate extract from the root of Sophora flavescens Ait. against focal cerebral ischemia in rats. Phytomedicine 2009;16:1042–1051.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhu XH, Qiu YD, Shi MK. Effect of matrine on cold ischemia and reperfusion injury of sinusoidal endothelial cells in rat orthotopic liver transplantation. Acta Pharmacol Sin 2003;24:169–174.PubMedGoogle Scholar
  20. 20.
    Zhang F, Mao Y, Qiao H, Jiang H, Tong L, Sun X. Protective effects of taurine against endotoxin-induced acute liver injury after hepatic ischemia reperfusion. Amino Acids 2010;38:237–245.PubMedCrossRefGoogle Scholar
  21. 21.
    Zhang F, Tong L, Qiao H, Jiang H, Tong L, Sun X. Taurine attenuates multiple organ injury induced by intestinal ischemia reperfusion in rats. J Surg Res 2008;149:101–109.PubMedCrossRefGoogle Scholar
  22. 22.
    Jiang H, Meng F, Li W, Tong L, Qiao H, Sun X. Splenectomy ameliorates acute multiple organ damage induced by liver warm ischemia reperfusion in rats. Surgery 2007;141:32–40.PubMedCrossRefGoogle Scholar
  23. 23.
    Tang B, Qiao H, Meng F, Sun X. Glycyrrhizin attenuates endotoxin-induced acute liver injury after partial hepatectomy in rats. Braz J Med Biol Res 2007;40:1637–1646.PubMedCrossRefGoogle Scholar
  24. 24.
    Tong L, Li J, Qiao H, Jiang H, Meng F, Sun X. Taurine protects against ischemia reperfusion injury in rabbit livers. Transplant Proc 2005;38:1575–1579.CrossRefGoogle Scholar
  25. 25.
    Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978;52:302–310.PubMedCrossRefGoogle Scholar
  26. 26.
    Zhao J, Yu S, Tong L, Jiang X, Pan S, Jiang H, et al. Oxymatrine attenuates intestinal ischemia reperfusion injury in rats. Surg Today 2008;38:931–937.PubMedCrossRefGoogle Scholar
  27. 27.
    Kong R, Sun B, Jiang H, Pan S, Chen H, Wang S, et al. Downregulation of nuclear factor-κB P65 subunit by small interfering RNA synergizes with gemcitabine to treat pancreatic cancer. Cancer Lett 2 2010;291:90–98.CrossRefGoogle Scholar
  28. 28.
    Tsuji K, Kwon AH, Yoshida H, Qiu Z, Kaibori M, Okumura T, et al. Free radical scavenger (edaravone) prevents endotoxininduced liver injury after partial hepatectomy in rats. J Hepatol 2005;42:94–101.PubMedCrossRefGoogle Scholar
  29. 29.
    Arii S, Shibagaki M, Takahashi S, Taki Y, Yokoo N, Jikko A, et al. Changes in the reticuloendothelial phagocytic function after partial hepatectomy. J Lab Clin Med 1985;105;668–672.PubMedGoogle Scholar
  30. 30.
    Kaibori M, Yanagida H, Uchida Y, Yokoigawa N, Kwon AH, Okumura T, et al. Pirfenidone protects endotoxin-induced liver injury after hepatic ischemia in rats. Transplant Proc 2004;36:1973–1974.PubMedCrossRefGoogle Scholar
  31. 31.
    Colletti LM, Green M. Lung and liver injury following hepatic ischemia/reperfusion in the rat is increased by exogenous lipopolysaccharide which also increases hepatic TNF production in vivo and in vitro. Shock 2001;16:312–319.PubMedCrossRefGoogle Scholar
  32. 32.
    Tsoulfas G, Takahashi Y, Ganster RW, Yagnik G, Guo Z, Fung JJ, et al. Activation of the lipopolysaccharide signaling pathway in hepatic transplantation preservation injury. Transplantation 2002;74:7–13.PubMedCrossRefGoogle Scholar
  33. 33.
    Sakaguchi T, Nakamura S, Suzuki S, Oda T, Ichiyama A, Baba S, et al. Participation of platelet-activating factor in the lipopolysaccharide-induced liver injury in partially hepatectomized rats. Hepatology 1999;30:959–967.PubMedCrossRefGoogle Scholar
  34. 34.
    Jiang H, Meng F, Li J, Sun X. Anti-apoptosis effects of oxymatrine protect livers from warm ischemia reperfusion injury in rats. World J Surg 2005;29:1397–1401.PubMedCrossRefGoogle Scholar
  35. 35.
    Jaeschke H. Reactive oxygen and mechanisms of inflammatory liver injury. J Gastroenterol Hepatol 2000;15:718–724.PubMedCrossRefGoogle Scholar
  36. 36.
    Kishimoto K, Hiraguri M, Koide N, Hanazaki K, Adachi W. Postoperative suppression of inflammatory cytokines after distal gastrectomy in elderly patients. Surg Today 2009;39:487–492.PubMedCrossRefGoogle Scholar
  37. 37.
    Dauphinee SM, Karsan A. Lipopolysaccharide signaling in endothelial cells. Lab Invest 2006;86:9–22.PubMedCrossRefGoogle Scholar
  38. 38.
    Su GL. Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation. Am J Physiol 2002;283:G256–G265.Google Scholar
  39. 39.
    Zampetaki A, Mitsialis SA, Pfeilschifter J, Kourembanas S. Hypoxia induces macrophage inflammatory protein-2 (MIP-2) gene expression in murine macrophages via NF-kappaB: the prominent role of p42/p44 and PI3 kinase pathways. FASEB J 2004;18:1090–1092.PubMedGoogle Scholar
  40. 40.
    Yao XM, Chen H, Li Y. Protective effect of bicyclol on liver injury induced by hepatic warm ischemia/reperfusion in rats. Hepatol Res 2009;39:833–842.PubMedCrossRefGoogle Scholar
  41. 41.
    Albelda SM, Smith CW, Ward PA. Adhesion molecules and inflammatory injury. FASEB J 1994;8:504–512.PubMedGoogle Scholar
  42. 42.
    Rentsch M, Post S, Palma P, Lang G, Menger MD, Messmer K. Anti-ICAM-1 blockade reduces postsinusoidal WBC adherence following cold ischemia and reperfusion, but does not improve early graft function in rat liver transplantation. J Hepatol 2000;32:821–828.PubMedCrossRefGoogle Scholar
  43. 43.
    Zwacka RM, Zhang Y, Zhou W, Halldorson J, Engelhardt JF. Ischemia/reperfusion injury in the liver of BALB/c mice activates AP-1 and nuclear factor kappaB independently of IkappaB degradation. Hepatology 1998;8:1022–1030.CrossRefGoogle Scholar
  44. 44.
    Streetz KL, Tacke F, Leifeld L, Wustefeld T, Graw A, Klein C, et al. Interleukin 6/gp130-dependent pathways are protective during chronic liver diseases. Hepatology 2003;38:218–229.PubMedCrossRefGoogle Scholar
  45. 45.
    Luedde T, Trautwein C. Intracellular survival pathways in the liver. Liver Int 2006;26:1163–1174.PubMedCrossRefGoogle Scholar
  46. 46.
    Streetz KL, Wustefeld T, Klein C, Kallen KJ, Tronche F, Betz UA, et al. Lack of gp130 expression in hepatocytes promotes liver injury. Gastroenterology 2003;125:532–543.PubMedCrossRefGoogle Scholar
  47. 47.
    Klein C, Wustefeld T, Assmus U, Roskams T, Rose-John S, Muller M, et al. The IL-6-gp130-STAT3 pathway in hepatocytes triggers liver protection in T cell-mediated liver injury. J Clin Invest 2005;115:860–869.PubMedGoogle Scholar
  48. 48.
    Li C, Jackson RM. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol 2002;282:C227–C241.PubMedGoogle Scholar
  49. 49.
    Chen HM, Chen MF, Shyr MH. Prostacyclin analogue (OP-2507) attenuates hepatic microcirculatory derangement, energy depletion, and lipid peroxidation in a rat model of reperfusion injury. J Surg Res 1998;80:333–338.PubMedCrossRefGoogle Scholar
  50. 50.
    Taylor BS, Geller DA. Molecular regulation of the human inducible nitric oxide synthase (iNOS) gene. Shock 2000;13:413–424.PubMedCrossRefGoogle Scholar
  51. 51.
    Albrecht EW, Stegeman CA, Heeringa P, Henning RH, van Goor H. Protective role of endothelial nitric oxide synthase. J Pathol 2003;199:8–17.PubMedCrossRefGoogle Scholar
  52. 52.
    Wink DA, Miranda KM, Espey MG, Pluta RM, Hewett SJ, Colton C, et al. Mechanisms of the antioxidant effects of nitric oxide. Antioxid Redox Signal 2001;3:203–213.PubMedCrossRefGoogle Scholar
  53. 53.
    Lin HI, Wang D, Leu FJ, Chen CF, Chen HI. Ischemia and reperfusion of liver induces eNOS and iNOS expression: effects of a NO donor and NOS inhibitor. Chin J Physiol 2004;47:121–127.PubMedGoogle Scholar
  54. 54.
    Hines IN, Kawachi S, Harada H, Pavlick KP, Hoffman JM, Bharwani S, et al. Role of nitric oxide in liver ischemia and reperfusion injury. Mol Cell Biochem 2002;234–235:229–237.PubMedCrossRefGoogle Scholar
  55. 55.
    Rudiger HA, Graf R, Clavien PA. Liver ischemia: apoptosis as a central mechanism of injury. J Invest Surg 2003;16:149–159.PubMedGoogle Scholar
  56. 56.
    Green DR. Apoptotic pathways: paper wraps stone blunts scissors. Cell 2000;102:1–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  • Feng Zhang
    • 1
  • Xun Wang
    • 2
  • Liquan Tong
    • 1
  • Haiquan Qiao
    • 3
  • Xinlei Li
    • 1
  • Liguang You
    • 1
  • Hongchi Jiang
    • 3
  • Xueying Sun
    • 3
  1. 1.Department of General Surgerythe Fifth Affiliated Hospital of Harbin Medical UniversityDaqingChina
  2. 2.Department of General SurgeryDaqing Oilfield General HospitalDaqingChina
  3. 3.Department of General Surgery, Hepatosplenic Surgery Centerthe First Affiliated Hospital of Harbin Medical UniversityHarbinChina

Personalised recommendations