Preoperative bombesin administration can protect the rat small bowel allograft from ischemic reperfusion injury

Abstract

Background/Purpose Ischemic reperfusion injury (IR/I) should be minimum for the success of small bowel transplantation (SBTx). This study investigated whether preoperative administration of neuropeptide bombesin (BBS) had a protective effect against IR/I and subsequent acute rejection. Methods Allogenic SBTx was performed heterotopically in rats (n = 18). All rats were administered FK506 (0.32 mg/kg per day) everyday. The rats were divided into 3 groups of 6 rats each: group 1, BBS(−)5: warm ischemic time (WIT), 5 minutes without BBS; group 2, BBS(−)15: WIT, 15 minutes without BBS; group 3, BBS(+)15: WIT, 15 minutes with BBS. The specimens were obtained from the stoma site at 1 hour after reperfusion and on postoperative day (POD) 1 and 7. The graft mucosal state and degree of acute rejection were evaluated by H&E staining. The apoptotic cells in the crypt lesion was evaluated using terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling immunohistochemistry. Apoptotic index (AI) was calculated for quantitative analysis. Results H&E staining revealed that the mucosal villi on POD 1 remained shortened in the BBS(−)15 group than in the other two groups. One hour after reperfusion, the AI in the BBS(−)15 group was 145.0‰ ± 37.2‰, which was significantly higher ( P < .05) than in the BBS(−)5 group (32.6‰ ± 5.0‰) or the BBS(+)15 group (32.0‰ ± 3.0‰). On POD 7, the AI in the BBS(−)15 group was 63.7‰ ± 5.03‰, which was significantly higher ( P < .05) than in the BBS(−)5 (17.3‰ ± 4.6‰) or the BBS(+)15 group (12.3‰ ± 3.06‰). Conclusions Even a short WIT of 15 minutes induced considerable allograft mucosal damage, which also worsened acute rejection. Exogenous BBS could prevent mucosal damage by IR/I and was also beneficial for the prevention of acute rejection.