title: Ulinastatin prevents acute lung injury led by liver transplantation.
abstract: BACKGROUND
  Little is known regarding the effect of ulinastatin (UTI) on acute lung injury (ALI) induced by orthotopic liver transplantation. This study aims to investigate the protective effect of UTI on ALI induced by orthotopic autologous liver transplantation (OALT) in a rat model and to explore the potential underlying mechanism.
  
  
  METHODS
  Rats were randomly allocated into the following four groups (n = 8 each): (i) sham control group (group sham); (ii) model group (underwent OALT) (group model); (iii) low-dose UTI-treated group (group u1), with UTI (50 U/g) administered intravenously both before the portal vein was occluded and after liver reperfusion started; and (iv) high-dose UTI-treated group (group uh), with UTI (100 U/g) given in the same way as group ul. The lung pathologic parameters, lung water content, and levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, malondialdehyde (MDA), superoxide dismutase (SOD) activity, RanBP-type and C3HC4-type zinc finger-containing protein 1 (RBCK1), and peroxiredoxin-2 (Prx-2) were assessed 8 h after OALT was performed.
  
  
  RESULTS
  According to histology, there was severe damage in the lung of group model accompanied by increases in the TNF-α, IL-1β, IL-6, and MDA levels and decreases in SOD activity and the expression of RBCK1 and Prx-2. UTI treatment significantly reduced the pathologic scores, lung water content, and TNF-α, IL-1β, IL-6, and MDA levels while restoring the SOD activity and expression of RBCK1 and Prx-2. Furthermore, compared with group u1, treatment with a high dose of UTI resulted in a better protective effect on the lung when assessed by the TNF-α, IL-1β, IL-6, and MDA levels and SOD activity.
  
  
  CONCLUSIONS
  UTI dose-dependently attenuates ALI that is induced by OALT in this rat model, which is mainly due to the suppression of the inflammatory response and oxidant stress, which may, in turn, be mediated by the upregulation of RBCK1 and Prx-2 expression.
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Gang-Jian
authors.initials: GJ
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Chen-Fang
authors.initials: CF
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address: heiziqing@sina.com.
authors.forename: Zi-Qing
authors.initials: ZQ
authors.lastname: Hei
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006023:Glycoproteins / Q000008:administration & dosage*; D018398:Homeodomain Proteins / Q000378:metabolism; D016031:Liver Transplantation / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011183:Postoperative Complications / Q000209:etiology / Q000517:prevention & control*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000008:administration & dosage*
chemical_list: D016207:Cytokines; D006023:Glycoproteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C586264:Prrx2 protein, rat; D014157:Transcription Factors; D014361:Trypsin Inhibitors; C489276:protein kinase C-binding protein Beta15, rat; D008315:Malondialdehyde; D013482:Superoxide Dismutase; C028665:urinastatin
keywords: Acute lung injury; OALT; Prx2; RBCK1; Ulinastatin