Attenuation of graft ischemia-reperfusion injury by urinary trypsin inhibitor in mouse intestinal transplantation.
OBJECTIVE
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. TNFalpha 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 TNFalpha and i-NOS mRNA was profoundly inhibited, while the infiltration of CD11b+ Gr1+ cells into the intestinal graft was decreased in UTI group.


CONCLUSIONS
Urinary trypsin inhibitor attenuates I/R injury in mouse intestinal transplantation by reducing monocytes infiltration and down-regulation of TNFalpha and i-NOS mRNA expression.
Yu
Ji-Ren
JR
Department of Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou 310003, Zhejiang Province, China. yansheng_cn@yahoo.com
Yan
Sheng
S
Liu
Xiao-Sun
XS
Wu
Yi-Jun
YJ
Fu
Pei-Feng
PF
Wu
Li-Hua
LH
Zheng
Shu-Sen
SS
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology / Q000637:transplantation*; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014361:Trypsin Inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D039481:CD11b Antigen; D006023:Glycoproteins; D012333:RNA, Messenger; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C028665:urinastatin