Long-term function and morphology of intestinal allografts in outbred canine transplantation model.
Long-term function and morphology of intestinal allografts in outbred canine transplantation model.
复制标题
远交犬移植模型中肠道同种异体移植物的长期功能和形态。
DOI：
10.1016/s0041-1345(02)02735-5
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发表时间：
2002
影响因子：
0.9
通讯作者：
Murase,N
中科院分区：
文献类型：
--
作者：
Iwanami,K;Ishikawa,T;Okuda,T;Zhu,Y;Tuerler,A;Moore,BA;Zhang,S;Bauer,AJ;Venkataramanan,R;Abu-Elmagd,K;Starzl,TE;Nalesnik,MA;Murase,N
材料和方法 14 只体重为 17 至 24 公斤、平均年龄为 22.6±3.1 个月的雌雄近交猎犬接受了整个小肠的原位移植，如前所述。 3 四名受者接受自体移植物（第 1 组）。 10 名同种异体 SBTx 接受者接受环孢素（CsA，20 至 30 mg/kg/天）治疗，并根据是否存在（第 2 组，n = 6）或存在（第 3 组，n = 4）临床症状（包括持续腹泻、厌食、营养不良和严重体重减轻）回顾性分为两组。自体和异体 SBTx 后 110 至 210 天，通过口服 CsA (10 mg/kg) 的药代动力学和 D-木糖吸收试验 (0.5 g/kg) 评估肠移植功能。肠道传输时间也通过钡 X 射线研究确定。此外，第1组和第2组的受者通过开放活检获得肠移植组织，第3组的受者通过处死获得肠移植组织。分析样品的肠刷状缘糖苷酶4活性、体外环肌机械活性测定5和组织病理学。以盲法对组织病理学变化进行分级。结果第 1 组（自身 SBTx）和第 2 组（无症状异源 SBTx）的受者在本研究时体重增加相当（移植前体重的 105%），血清总蛋白和胆固醇水平令人满意（表 1）。相比之下，第 3 组的受者在 SBTx 后 30 至 40 天出现严重腹泻，尽管食欲旺盛，但仍出现营养不良和体重显着下降（移植前体重的 76.5%）。 SBTx后4至7个月时，第1组和第2组的受体的肠道通过时间为185分钟，略短于正常未手术犬；但第 3 组的时间大大缩短至 60±30 分钟。 CsA 的药代动力学与总体接受者营养状况相关：第 1 组和第 2 组中 CsA 的血峰浓度（Cmax，ng/mL）和曲线下面积（AUC，ng×h/mL）与正常未手术犬中观察到的相当。相反，第3组的D-木糖吸收显着下降。与正常动物相比，所有组中的D-木糖吸收均较差；特别是，第 3 组的接受者减少了 65.3%。这些结果表明，第 2 组同种异体移植肠道和第 1 组自体移植肠道的长期功能相当，而第 3 组同种异体移植肠道功能受损。
MATERIALS AND METHODSFourteen outbred hound dogs of both sexes weighing 17 to 24 kg with the mean age of 22.6±3.1 months underwent orthotopic transplantation of the entire small bowel as previously described. 3 Four recipients received autologous grafts (Group 1). Ten recipients of allogeneic SBTx were treated with cyclosporine (CsA, 20 to 30 mg/kg/day) and retrospectively divided into two groups according to the absence (Group 2, n= 6) or presence (Group 3, n= 4) of clinical symptoms, including continuous diarrhea, anorexia, malnutrition, and severe body weight loss. Between 110 and 210 days after auto-and allo-SBTx, intestinal graft function was evaluated by pharmacokinetics of oral CsA (10 mg/kg) and D-xylose absorption test (0.5 g/kg). Intestinal transit time was also determined by a barium X-ray study. In addition, intestinal graft tissues were obtained by open biopsy in recipients of Groups 1 and 2 and by sacrifice in Group 3. Samples were analyzed for intestinal brush border glycosidase 4 activity, in vitro circular muscle mechanical activity assay, 5 and histopathology. Histopathological changes were graded with a blinded fashion.RESULTSRecipients in Groups 1 (auto-SBTx) and 2 (allo-SBTx without symptoms) had comparable body weight gain by the time of this study (105% of pretransplant weight) with satisfactory serum total protein and cholesterol levels (Table 1). In contrast, recipients in Group 3 developed severe diarrhea 30 to 40 days after SBTx and suffered from malnutrition and significant body weight loss (76.5% of pretransplant weight) in spite of their voracious appetite. Intestinal transit time of recipients in Groups 1 and 2 at 4 to 7 months after SBTx was 185 minutes, slightly shorter than that of normal unoperated dogs; but it was extremely shortened to 60±30 minutes in Group 3. Pharmacokinetics of CsA correlated well with overall recipient nutritional condition: peak blood concentration (Cmax, ng/mL) and area under the curve (AUC, ng× h/mL) of CsA in Groups 1 and 2 were comparable to those seen in normal unoperated dogs. In contrast, they were significantly decreased in Group 3. D-xylose absorption was inferior in all groups compared to normal animals; especially, recipients in Group 3 showed 65.3% reduction. These results indicated comparable long-term function of intestinal allografts in Group 2 and auto grafts in Group 1, and impaired intestinal function in Group 3 allografts.