Induction of heme oxygenase-1 improves the survival of pancreas grafts by prevention of pancreatitis after transplantation

被引:28
作者
Becker, Thomas [1 ]
Vilsendorf, Andreas Meyer zu [1 ]
Terbish, Talvankhuu [1 ]
Klempnauer, Jurgen [1 ]
Joerns, Anne [2 ,3 ]
机构
[1] Hannover Med Sch, Dept Gen Visceral & Transplant Surg, D-3000 Hannover, Germany
[2] Hannover Med Sch, Inst Clin Biochem, D-3000 Hannover, Germany
[3] Hannover Med Sch, Ctr Anat, D-3000 Hannover, Germany
关键词
pancreas transplantation; heme oxygenase-1; graft pancreatitis; reperfusion injury;
D O I
10.1097/01.tp.0000290233.81395.81
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Ischemia/reperfusion (I/R) injury after pancreas transplantation might result in graft pancreatitis. The role of heme oxygenase-1 (HO-1) in pancreas transplantation and prevention of graft pancreatitis is unknown. Method. We studied the impact of HO-1 induction with cobalt protoporphyrin (CoPP) in experimental pancreas transplantation with moderate (6 hr) and prolonged (20 hr) cold ischemic time (CIT). Donor animals received CoPP 5 mg/kg intraperitoneal at 48 hr or intraperitoneal saline injections in the corresponding control groups before procurement. Harvested grafts were perfused with HTK solution and stored at 4 degrees C. Results. After prolonged CIT, graft survival was 100% with CoPP pretreatment in contrast to only 37.5% without pretreatment. CoPP-pretreated grafts demonstrated an unimpaired endocrine graft function at moderate and prolonged CIT. Serum lipase activity as a sign of exocrine preservation was significantly lower. In addition, morphological architecture was well preserved. Copp pretreatment markedly increased HO-I gene expression in donor pancreas (130-fold increase) by means of quantitative reverse transcriptase -polymerase chain reaction. Immunohistochemical examinations showed that the increase of HO-1 on the protein level was related to HO-1-positive donor macrophages in the pancreas grafts. HO-1 overexpression was accompanied by significant decrease of proinflammatory cytokines such as tumor necrosis factor-a, interleukin (IL)-2, IL-6, interferon-y, and by significant increase of the anti-inflammatory cytokine IL-10 and less expression of adhesion molecules such as e- and p-selectins. Conclusions. HO-1 is highly inducible in the allograft rat pancreas and associated with a survival benefit and good graft function after transplantation. This study contributes to the beneficial potentials of HO-1 for the prevention of graft pancreatitis.
引用
收藏
页码:1644 / 1655
页数:12
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