PURPOSE: In small bowel transplantation, the bowel graft is susceptible to reperfusion injury. This study investigated the effects of tetrandrine, a bisbenzylisoquinoline alkaloid, on the development of intestinal reperfusion injury in small bowel transplantation in pigs. MATERIALS AND METHODS: Pigs underwent small bowel transplantation and were treated with tetrandrine or a vehicle. Blood and small bowel specimens were harvested at 1, 3, and 24 hours after reperfusion. Histopathologic analysis of the small bowel was assessed for tissue damage. Serum levels of tumor necrosis factor-alpha, interleukin-1beta (IL-1beta), and IL-6 were measured by enzyme-linked immunosorbent assay. Reverse-transcriptase polymerase chain reaction analysis was performed to analyze the expression of proinflammatory cytokines, and immunohistochemical analysis was used to study the expression of intercellular adhesion molecule-1 (ICAM-1) in the small bowel. Myeloperoxidase staining detected neutrophil infiltration in the small bowel and the number of myeloperoxidase positively stained cells was counted. RESULTS: Pigs receiving small bowel transplantation had elevated serum proinflammatory cytokine levels. The transplanted small bowel showed mucosal damage, increased expression of proinflammatory cytokines and ICAM-1, and prominent neutrophil infiltration. Tetrandrine administration reduced mucosal damage, serum and tissue proinflammatory cytokine levels, ICAM-1 expression, and neutrophil accumulation in the transplanted small bowel. CONCLUSIONS: Tetrandrine reduced the reperfusion injury in porcine intestinal transplantation during the first 24 hours after the procedure.
PURPOSE: In small bowel transplantation, the bowel graft is susceptible to reperfusion injury. This study investigated the effects of tetrandrine, a bisbenzylisoquinoline alkaloid, on the development of intestinal reperfusion injury in small bowel transplantation in pigs. MATERIALS AND METHODS:Pigs underwent small bowel transplantation and were treated with tetrandrine or a vehicle. Blood and small bowel specimens were harvested at 1, 3, and 24 hours after reperfusion. Histopathologic analysis of the small bowel was assessed for tissue damage. Serum levels of tumor necrosis factor-alpha, interleukin-1beta (IL-1beta), and IL-6 were measured by enzyme-linked immunosorbent assay. Reverse-transcriptase polymerase chain reaction analysis was performed to analyze the expression of proinflammatory cytokines, and immunohistochemical analysis was used to study the expression of intercellular adhesion molecule-1 (ICAM-1) in the small bowel. Myeloperoxidase staining detected neutrophil infiltration in the small bowel and the number of myeloperoxidase positively stained cells was counted. RESULTS:Pigs receiving small bowel transplantation had elevated serum proinflammatory cytokine levels. The transplanted small bowel showed mucosal damage, increased expression of proinflammatory cytokines and ICAM-1, and prominent neutrophil infiltration. Tetrandrine administration reduced mucosal damage, serum and tissue proinflammatory cytokine levels, ICAM-1 expression, and neutrophil accumulation in the transplanted small bowel. CONCLUSIONS:Tetrandrine reduced the reperfusion injury in porcine intestinal transplantation during the first 24 hours after the procedure.