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Article Navigation >  Journal of Pharmaceutical Practice and Service  > 2014  >  32(2): 110-113,127

LIN Feng, ZHOU Zhijun, ZHANG Chenhong, LIU Fang, GUO Wenyuan, WEI Ruohan, CHEN Hui. Alleviation of reperfusion injury for liver graft via inhibiting inflammatory response by ulinastatin[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(2): 110-113,127. doi: 10.3969/j.issn.1006-0111.2014.02.009
Citation: LIN Feng, ZHOU Zhijun, ZHANG Chenhong, LIU Fang, GUO Wenyuan, WEI Ruohan, CHEN Hui. Alleviation of reperfusion injury for liver graft via inhibiting inflammatory response by ulinastatin[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(2): 110-113,127. doi: 10.3969/j.issn.1006-0111.2014.02.009
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Alleviation of reperfusion injury for liver graft via inhibiting inflammatory response by ulinastatin

doi: 10.3969/j.issn.1006-0111.2014.02.009
  • 1.

    The First People's Hospital of Taizhou, Taizhou 318020, China

  • 2.

    Organ Transplantation Center, Changzheng Hospital Afilliated to Second Military Medical University, Shanghai 200003, China

  • Received Date: 2012-04-29
  • Rev Recd Date: 2013-04-17
  • Objective To evaluate the protective effect of ulinastatin on reperfusion injury of liver graft in rats and the related mechanisms. Methods The orthotopic liver transplantation (OLT) model between syngeneic Sprague-Dawley rats was used, and recipient rats were allocated in three groups:sham operation (SO) group, control group, and ulinastatin (UTI) group. Just after OLT procedure, rats in UTI group received ulinastatin injection at a dose of 1×104 IU/kg by tail vein, and rats in control group received saline injection with equal dose. Four rats at 6 hour and the others at 24 hour after OLT were sacrificed; the sera and liver were collected. The ALT levels in serum were detected and hepatic histological changes and hepatocellular apoptosis were examined. The infiltration of Kupffer cells was detected by immunochemistry analysis, and the relative mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and monocyte chemoattractant protein (MCP)-1 in the liver tissue and the content of these cytokines in the sera were measured with real time PCR and ELISA. The activation of transcription factor NF-κB was measured with Western blotting analysis. Results Compared with the rats in control group, at the same time-point rats in UTI group exhibited lower levels of ALT (P<0.01), better hepatic histological changes (P<0.01), less hepatocellular apoptosis (P<0.01), lower mRNA expression of TNF-α, IL-6, IL-1β and MCP-1 in the liver tissue and lower content of these cytokines in the sera (P<0.01). Moreover, the activation of NF-κB in UTI group was significantly down-regulated in comparison with that in control group. Conclusion Ulinastatin could reduce reperfusion injury for liver graft via inhibiting inflammatory response and deserve deep research as novel protective agent.
  • [1] Song S, Shen X, Tang Y, et al. Sinomenine pretreatment attenuates cold ischemia/reperfusion injury in rats:the role of heme oxygenase-1[J]. Int Immunopharmacol, 2010, 10(6):679.
    [2] Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method[J]. Methods, 2001, 25(4):402.
    [3] Suzuki S, Toledo-Pereyra LH, Rodriguez FJ, et al. Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine[J]. Transplantation,1993, 55(6):1265.
    [4] Dogan S, Aslan M. Hepatic ischemia-reperfusion injury and therapeutic strategies to alleviate cellular damage[J]. Hepatol Res,2011, 41(2):103.
    [5] Bhogal RH, Sutaria R, Afford SC. Hepatic liver ischemia/reperfusion injury:processes in inflammatory networks—a review[J]. Liver Transpl, 2011,17(1):95.
    [6] Yamanouchi K, Eguchi S, Kamohara Y, et al. Glycine reduces hepatic warm ischaemia-reperfusion injury by suppressing inflammatory reactions in rats[J]. Liver Int, 2007, 27(9):1249.
    [7] Umeadi C, Kandeel F, Al-Abdullah IH. Ulinastatin is a novel protease inhibitor and neutral protease activator[J]. Transplant Proc, 2008, 40(2):387.
    [8] 郑继海, 王金彩, 卢光洲. 乌司他丁与奥曲肽治疗急性胰腺炎的经济学评价[J].药学实践杂志, 2005, 23(2):103.
    [9] Hou J, Zhu MW, He XW, et al. Effect of hyperbaric oxygen and ulinastatin on plasma endotoxin, soluble CD14, endotoxin-neutralizing capacity and cytokines in acute necrotizing pancreatitis[J]. Can J Surg, 2010, 53(4):241.
    [10] Park KH, Lee KH, Kim H, et al. The anti-inflammatory effects of ulinastatin in trauma patients with hemorrhagic shock[J]. J Korean Med Sci, 2010, 25(1):128.
    [11] Wanner GA, Ertel W, Müller P, et al. Liver ischemia and reperfusion induces a systemic inflammatory response through Kupffer cell activation[J]. Shock,1996,5(1):34.
    [12] 郭闻渊, 滕飞, 宋少华, 等. 丹参多酚酸盐抑制库普弗细胞活化减轻肝脏再灌注损伤[J]. 上海医学, 2010, 33(7):644.
    [13] Shiratori Y, Kiriyama H, Fukushi Y, et al. Modulation of ischemia-reperfusion-induced hepatic injury by Kupffer cells[J]. Dig Dis Sci, 1994, 39(6):1265.
    [14] Hisama N, Yamaguchi Y, Ishiko T, et al. Kupffer cell production of cytokine-induced neutrophil chemoattractant following ischemia/reperfusion injury in rats[J]. Hepatology, 1996, 24(5):1193.
    [15] Bezinover D, Kadry Z, McCullough P, et al. Release of cytokines and hemodynamic instability during the reperfusion of a liver graft[J]. Liver Transpl, 2011,17(3):324.
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Alleviation of reperfusion injury for liver graft via inhibiting inflammatory response by ulinastatin

doi: 10.3969/j.issn.1006-0111.2014.02.009
  • 1. The First People's Hospital of Taizhou, Taizhou 318020, China
  • 2. Organ Transplantation Center, Changzheng Hospital Afilliated to Second Military Medical University, Shanghai 200003, China
  • Received Date: 2012-04-29
  • Rev Recd Date: 2013-04-17

Abstract: Objective To evaluate the protective effect of ulinastatin on reperfusion injury of liver graft in rats and the related mechanisms. Methods The orthotopic liver transplantation (OLT) model between syngeneic Sprague-Dawley rats was used, and recipient rats were allocated in three groups:sham operation (SO) group, control group, and ulinastatin (UTI) group. Just after OLT procedure, rats in UTI group received ulinastatin injection at a dose of 1×104 IU/kg by tail vein, and rats in control group received saline injection with equal dose. Four rats at 6 hour and the others at 24 hour after OLT were sacrificed; the sera and liver were collected. The ALT levels in serum were detected and hepatic histological changes and hepatocellular apoptosis were examined. The infiltration of Kupffer cells was detected by immunochemistry analysis, and the relative mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and monocyte chemoattractant protein (MCP)-1 in the liver tissue and the content of these cytokines in the sera were measured with real time PCR and ELISA. The activation of transcription factor NF-κB was measured with Western blotting analysis. Results Compared with the rats in control group, at the same time-point rats in UTI group exhibited lower levels of ALT (P<0.01), better hepatic histological changes (P<0.01), less hepatocellular apoptosis (P<0.01), lower mRNA expression of TNF-α, IL-6, IL-1β and MCP-1 in the liver tissue and lower content of these cytokines in the sera (P<0.01). Moreover, the activation of NF-κB in UTI group was significantly down-regulated in comparison with that in control group. Conclusion Ulinastatin could reduce reperfusion injury for liver graft via inhibiting inflammatory response and deserve deep research as novel protective agent.

LIN Feng, ZHOU Zhijun, ZHANG Chenhong, LIU Fang, GUO Wenyuan, WEI Ruohan, CHEN Hui. Alleviation of reperfusion injury for liver graft via inhibiting inflammatory response by ulinastatin[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(2): 110-113,127. doi: 10.3969/j.issn.1006-0111.2014.02.009
Citation: LIN Feng, ZHOU Zhijun, ZHANG Chenhong, LIU Fang, GUO Wenyuan, WEI Ruohan, CHEN Hui. Alleviation of reperfusion injury for liver graft via inhibiting inflammatory response by ulinastatin[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(2): 110-113,127. doi: 10.3969/j.issn.1006-0111.2014.02.009
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