Attenuation of graft ischemia-reperfusion injury by urinary trypsin inhibitor in mouse intestinal transplantation

AIM: Ischemia/reperfusion (I/R) injury is one of the major obstacles for intestinal transplantation (ITx). Urinary trypsin inhibitor (Ulinastatin, UTI) suppresses proteases and stabilizes lysosomal membranes. We supposed that Ulinastatin would diminish I/R injury of intestinal graft. METHODS: UTI-treated group and untreated control group were investigated by histological assessment at 1.5, 4, 24, and 72 h after ITx. Myeloperoxidase (MPO) activity was used as the activity of neutrophils, and malondialdehyde (MDA) was used as an index of lipid peroxidation. TNF alpha and i-NOS mRNA expression in graft tissue were measured by semi-quantitative RT-PCR. CD11b(+) Gr1(+) cells in graft lamina propria were analyzed by flow cytometry. RESULTS: Histological scores of the graft showed that the tissue injury was markedly attenuated by UTI treatment at different time points after ITx, with reduced MPO and MDA value in the grafts. The expression of TNF alpha and i-NOS mRNA was profoundly inhibited, while the infiltration of CD11b(+) Gr1(+) cells into the intestinal graft was decreased in UTI group. CONCLUSION: Urinary trypsin inhibitor attenuates I/R injury in mouse intestinal transplantation by reducing monocytes infiltration and down-regulation of TNF alpha and i-NOS mRNA expression. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.