Kellersman R, Zhong R, Kiyochi H, Garcia B, Grant D R
The University of Western Ontario, Department of Surgery, London Health Sciences Centre, Ontario, Canada.
Transplantation. 2000 Jan 15;69(1):10-6. doi: 10.1097/00007890-200001150-00003.
The surgical procedure of small bowel transplantation normally results in complete disruption of the graft's lymphatic drainage. The present study was undertaken to determine the impact of lymphatic reconstruction (LR) on the outcome of intestinal grafting, using a microsurgical model that immediately restores lymphatic drainage.
Brown Norway (RT1n) intestinal grafts were orthotopically transplanted into Lewis (RT1(1)) rats either with LR (+LR) or without LR (-LR). Recipients were randomly allocated into the following groups: no treatment or cyclosporine (CsA) at a dose of 2, 5, or 10 mg/kg/day subcutaneously from postoperative day (POD) 0 to 6.
There was morphological regeneration of lymphatics in the -LR group between 1-3 weeks as previously reported, whereas normal lymph flow was immediately restored in the +LR group. All untreated and CsA(2 mg)-treated allografts were rapidly rejected in both the +LR and -LR groups. In the groups treated with approximately 5 mg of CsA, five of six -LR animals died of chronic rejection between 38 and 86 days (mean survival time +/- SD: 76.7+/-21 days), while all +LR animals survived until death on POD 100 (P < 0.05). Histological features of mucosal damage found in -LR grafts were absent in the +LR grafts. All of the animals treated with 10 mg of CsA survived indefinitely. Sequential histology revealed mild rejection in -LR and +LR grafts on POD 45, but +LR animals had significantly higher body weight gains (POD 50: -LR: 117+/-12% vs. +LR: 136+/-4%, P < 0.01). LR did not affect donor cell migration and nutritional parameters.
LR improves the long-term results of small bowel transplantation resulting in better survival rates, less mucosal damage due to chronic graft rejection, and greater weight gain. We conclude that impairment of lymph flow may contribute to poor outcomes when standard surgical techniques are used for small bowel transplantation.
小肠移植手术通常会导致移植物淋巴引流完全中断。本研究采用一种能立即恢复淋巴引流的显微手术模型,以确定淋巴重建(LR)对肠道移植结果的影响。
将棕色挪威(RT1n)品系大鼠的肠移植物原位移植到刘易斯(RT1(1))品系大鼠体内,分为进行淋巴重建(+LR)组和未进行淋巴重建(-LR)组。受体大鼠被随机分为以下几组:不进行处理或从术后第0天(POD)至第6天皮下注射剂量为2、5或10mg/kg/天的环孢素(CsA)。
如先前报道,-LR组在1至3周内淋巴管出现形态学再生,而+LR组立即恢复了正常淋巴流动。在+LR组和-LR组中,所有未处理及接受2mg CsA处理的同种异体移植物均迅速被排斥。在接受约5mg CsA处理的组中,-LR组的6只动物中有5只在38至86天之间死于慢性排斥(平均生存时间+/-标准差:76.7+/-21天),而所有+LR组动物均存活至POD 100时自然死亡(P<0.05)。+LR组移植物未出现-LR组移植物中发现的黏膜损伤组织学特征。所有接受10mg CsA处理的动物均无限期存活。连续组织学检查显示,POD 45时-LR组和+LR组移植物均出现轻度排斥,但+LR组动物体重增加明显更高(POD 50时:-LR组:117+/-12% vs. +LR组:136+/-4%,P<0.01)。淋巴重建不影响供体细胞迁移和营养参数。
淋巴重建改善了小肠移植的长期结果,提高了生存率,减少了慢性移植物排斥导致的黏膜损伤,并使体重增加更多。我们得出结论,当采用标准手术技术进行小肠移植时,淋巴流动受损可能导致不良结果。