RESUMO
Severe graft rejection remains an important obstacle in intestinal transplantation. In this study, dendritic cells (DCs) isolated from rat bone marrow were cultured for 5 days, and triptolide applied for 3 more days. The recipient rats were pretreated with donor triptolide-modified or not modified DC. Small bowel transplantation was performed to observed survival times. We demonstrated that triptolide markedly inhibited both the expression of CD80 and MHCII expression on DCs. Triptolide-modified DCs stimulated lower proliferative responses among allogeneic T cells, prolonging the survival of intestinal allografts in rats. These results suggested that pretreatment with triptolide-modified DC prolonged the survival of rat small bowel allografts after transplantation.
Assuntos
Células Dendríticas/imunologia , Células Dendríticas/transplante , Diterpenos/uso terapêutico , Sobrevivência de Enxerto/fisiologia , Imunossupressores/uso terapêutico , Intestino Delgado/transplante , Fenantrenos/uso terapêutico , Animais , Antígeno B7-1/imunologia , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Células Dendríticas/efeitos dos fármacos , Compostos de Epóxi/uso terapêutico , Sobrevivência de Enxerto/efeitos dos fármacos , Antígenos de Histocompatibilidade Classe II/imunologia , Ativação Linfocitária , Teste de Cultura Mista de Linfócitos , Masculino , Ratos , Ratos Endogâmicos WF , Ratos Sprague-Dawley , Linfócitos T/imunologia , Transplante Homólogo/imunologiaRESUMO
In order to facilitate preclinical research, we established a new combined liver-small bowel transplantation rat model. Male inbred Wistar rats were chosen as donors and recipients. An en bloc liver-small bowel graft was harvested. During the donor operation, the inferior vena cava in the chest was removed to be used as an interpositional venous graft to anastomose to the portal vein. In the recipient operation the portal veins of donor and recipient were quickly anastomosed using a cuff technique instead of the traditional suture method. Rearterialization was achieved by anastomosing the superior mesenteric artery of graft to the right renal artery of the recipient. The recipient small bowel was resected and intestinal continuity restored simultaneously by two end-to-end anastomoses. The postoperative 5-day survival rate was 77.5% (31/40) and 60-day survival rate, 72.5% (29/40). Recipient rats that tolerated the operation remained healthy. Liver and renal function was normal. The liver and intestinal grafts showed normal histological architecture in all rats surviving for 2 months postoperatively. Our results demonstrated that the present model is feasible, allowing preclinical experimental research on combined liver-small bowel transplantation.
Assuntos
Intestino Delgado/transplante , Transplante de Fígado , Transplante Isogênico/métodos , Animais , Sobrevivência de Enxerto , Masculino , Artéria Mesentérica Superior/cirurgia , Modelos Animais , Veia Porta/cirurgia , Ratos , Ratos Wistar , Veia Cava Inferior/cirurgiaRESUMO
Immune tolerance promises to enhance allograft survival while reducing risks inherent to immunosuppressants. In this study, we evaluated the effect of interleukin (IL)-12p35 silenced dendritic cells (DC) combined with cyclosporine (CsA) on induction of immune tolerance in intestinal transplantation. The results showed that combination treatment with donor IL-12p35 silenced DC and a low dose of CsA (8 mg/kg) prolonged rat intestinal allograft survival. However, a higher dose of CsA (20 mg/kg) did not further prolong allograft survival.