大鼠肝肠联合移植后肝对小肠的免疫保护作用

Immuno-protective effect of liver on small bowel in combined transplantation of liver and small bowel

目的：建立大鼠肝肠联合整体移植模型,研究移植肝是否对移植小肠具有免疫保护作用．方法：选用封闭群SD大鼠和近交系Wistar大鼠．实验分5组：同基因小肠移植组、同基因肝移植组、异基因小肠移植组、异基因肝移植组、肝肠联合移植组．同基因移植供受体均为Wistar大鼠,异基因小肠移植、肝移植和肝肠联合移植供受体分别选用SD和Wistar大鼠．肝肠联合移植在切取移植物后,利用供体胸段下腔静脉在门静脉侧壁建立一袖套,并安置套管．受体手术时,将此门静脉侧壁袖套与受体门静脉残端套管法吻合．供体肠系膜上动脉与受体右肾动脉吻合．免疫保护作用通过术后5,7,14 d从各组随机取出4只大鼠的移植物普通病理检查及细胞凋亡检测评估．结果：肝肠联合移植模型建立手术成功率73．3%(22/30)．同基因移植组术后仅表现为缺血-再灌注损伤所致的轻度组织损伤及炎症反应,移植物细胞凋亡数逐渐减少．异基因移植术后均出现急性排斥、移植物细胞凋亡数递增,并且较同基因移植多,差别有显著性．小肠移植术后5,7,14 d分别表现为轻度、中度和重度排斥．而肝肠联合移植的小肠移植物术后5,7,14 d分别表现为轻度、轻度和中度排斥,且14 d时小肠细胞凋亡数较异基因小肠移植组少,差别具有显著性(16．9±4．3 vs 20．5±6．3,P＜0．05)．术后各时间点异基因肝移植和肝肠联合移植的移植肝排斥反应严重程度相同,细胞凋亡数比较无显著差异．结论：此法建立大鼠肝肠联合移植模型可行．肝肠联合移植时肝对小肠具有免役保护作用．

AIM： To develop a new combined transplantation model of liver and small bowel in rats, and to investigate the protective effect of transplanted liver on transplanted small bowel. METHODS： Closed colony Sprague Dawley rats and inbred Wistar rats were included in this study. Five groups were designed： isogene small bowel transplant group （A）, isogene liver transplant group （B）, xenogene small bowel transplant group （C）, xenogene liver transplant group （D）, combined transplant of liver and small bowel group （E）. Only Wistar rats were used in group A and B, while SD and Wistar rats were used as donors and recipients respectively in group C, D and E. During the combined transplantation of liver and small bowel （CTLS） for the donors, inferior vena cava in chest was cut to construct a muff in the lateral wall of portal vein and cuff was placed. During the operation for the recipients, portal veins of the donors and recipients were connected using cuff technique, and re-arterialization was completed by anastomosing the superior mesenteric artery of graft with the right kidney artery of the recipients. Randomly selected 4 rats from each group were sacrificed on postoperative days （POD） 5, 7 and 14, and grafts were sampled. The rejection of graft was investigated through histopathological analysis, and the apoptosis of the cells of graft were evaluated by TUNEL. RESULTS： The survival rate of CTLS was 73.3% （22/30）. The pathological changes of ischemia and reperfusion injury were observed in group A and B, and the numbers of apoptotic cells in the grafts were decreased with the prolonging of time. However, acute rejection after transplantation appeared in group C and D, and there were more apoptotic cells in the grafts. Mild, moderate and severe acute rejection occurred on POD 5, 7 and 14, respectively in group C, while only mild or severe acute rejection appeared in group E. Furthermore, the number of apoptotic cells in the grafts of group E was markedly decreased on POD 14 in comparison with that of group C （16.9±4.3 vs 20.5±6.3, P 〈 0.05）. The degrees of acute rejection after transplantation and cell apoptosis of the grafts were not significantly different between group D and E. CONCLUSION： The technique used in this study is feasible for establishment of CTLS model, and the transplanted liver can protect the transplanted intestinal graft from rejection in CTLS.