Cyclooxygenase Inhibitors as a New Therapeutic Strategy in Small Bowel Transplantation

被引：5

作者：

Schildberg, Frank Alexander ^{[1
,4
]}

Liu, Bin ^{[1
,5
]}

Afify, Mamdouh ^{[1
,6
]}

Steitz, Julia ^{[1
]}

Paschenda, Pascal ^{[1
]}

Schaefer, Nico ^{[2
]}

Kalff, Joerg C. ^{[2
]}

Minor, Thomas ^{[3
]}

Tolba, Rene Hany ^{[1
]}

机构：

[1] Rhein Westfal TH Aachen, Inst Lab Anim Sci & Expt Surg, Pauwelsstr 30, D-52074 Aachen, Germany

[2] Univ Bonn, Dept Surg, Med Ctr, Bonn, Germany

[3] Univ Bonn, Med Ctr, Div Surg Res, Dept Surg, Bonn, Germany

[4] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA

[5] Huazhong Univ Sci & Technol, Tongji Hosp, Inst Organ Transplantat, Wuhan, Peoples R China

[6] Cairo Univ, Dept Pathol, Fac Vet Med, Giza, Giza Governorat, Egypt

来源：

TRANSPLANTATION | 2016年 / 100卷 / 11期

关键词：

ISCHEMIA-REPERFUSION INJURY; SMOOTH-MUSCLE DYSFUNCTION; NITRIC-OXIDE SYNTHASE; INTESTINAL TRANSPLANTATION; POSTOPERATIVE ILEUS; ISCHEMIA/REPERFUSION INJURY; CYCLO-OXYGENASE-2; GENE; RESIDENT MACROPHAGES; ENDOTHELIAL-CELLS; UP-REGULATION;

D O I：

10.1097/TP.0000000000001317

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. The long-term outcome of intestinal transplantations is still not favorable, which is partly due to the intestinal susceptibility to ischemia. There are several indications that the inflammatory response to ischemia-reperfusion injury is mediated by cyclooxygenases and that their inhibition may be associated with improved organ function. The aim of this study was to analyze if cyclooxygenase (COX) inhibitors could improve the early posttransplant outcome after orthotopic small bowel transplantation. Methods. Small bowel transplantation was performed between rats to test the impact of nonselective (Piroxicam), preferential (Meloxicam), and selective COX-2 inhibitors (Parecoxib). The donor intestines were either perfused and stored with inhibitor or had inhibitor administered intravenously after transplantation. Results. Using COX inhibitors, a sequential increase of posttransplantation intestinal integrity could be shown, with Parecoxib the least effective andMeloxicamthemost effective treatment. These differences were in line with the downregulation of COX-2 activity by the inhibitors. Functionally, the same tendency could be seen in diminished expression of proinflammatory molecules, decreased leucocyte inflammation, and significantly improved graftmicrocirculation. In most cases, the intravenous administration was more effective. However, the COX inhibitors used were shown to cause relevant hepatotoxicity under nearly all conditions, but particularly under intravenous administration. Only Meloxicam in histidine-tryptophan-ketoglutarate was demonstrated to be a safe drug without hepatotoxic side effects. Conclusions. The activity of COX contributes to ischemia-reperfusion injury after intestinal transplantation. In this comparative study, the administration of the preferential COX-2 inhibitor Meloxicam via histidine-tryptophan-ketoglutarate showed the best graft-protective attributes and the lowest hepatotoxic side effects.

引用

页码：2324 / 2331

页数：8

共 47 条

[1] Intestinal transplantation for short bowel syndrome and gastrointestinal failure: Current consensus, rewarding outcomes, and practical guidelines [J].