Experimental study of kidney xenografting using small and middle animals

中小动物肾异种移植的实验研究

基本信息

批准号：
01570910
负责人：
SUZUKI Seiichi
金额：
$ 1.22万
依托单位：
National Cardiovascular Center Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至无数据
项目状态：
已结题

项目摘要

We studied the preventive effect of a novel immunosuppressant, 15-deoxyspergualin(DSG), on graft rejection in kidney xenotransplantation. In rodent model, hamsters and rats were used as donors and recipients, respectively. The left kidney was removed from donor with aorta and inferior vena cava, and the proximal ends of these vessels were ligated. The anastomosis of the donor artery and vein were performed with end-to-side manners to the recipient abdominal aorta and inferior vena cava. The recipient kidneys were simultaneously removed immediately after the grafting. Donor ureter was anastomosed by the method of vesiculo-vesiculal neostomy. The control rats, treated with no immunosuppressant, died on 3.3<plus-minus>0.5 days(n=6), DSG 5mg/kg/day-treated rats died on 6.0<plus-minus>2.0 days(n=4), and DSG 10mg/kg/day-treated rats died on 9.0<plus-minus>6.3 days(n=5). When statistically analyzed, recipient survival in the both DSG-treated groups were shown to be significant from that in th … More e control group. The best graft survival was observed in the group treated with DSG at a dose of 10 mg/kd/day. However, two rats died on day 3 and 5, respectively, in the 10 mg/kg/day-treated group. This may indicate that higher dose of DSG has a toxic effect on xenografted recipients. Therefore, we used DSG at a dose of 5 mg/kg/day in the experimental model of kidney transplantation from rabbits to rats. In this model, the recipients died on days 3,4,4,5 in the control group and on days 4,4,4,5 in the DSG-treated group. There was no significant difference between these two gOn the other hand, in the rat cardiac allograft model, we immunized donor antigen in the pre-transplant recipient to expand the donor specific lymphocyte clones, and then the recipient was treated with DSG to eliminate these specific clones and to induce the immunological unresponsiveness. It was demonstrated that 60% of the recipients acquired imunological unresponsiveness by the above-mentioned treatment. We are now applying this method in the rodent xenografting for induction of long survival of kidney recipients. Less

我们研究了一种新型免疫抑制剂15-脱氧精胍菌素（DSG）对肾异种移植中移植物排斥反应的预防作用，在啮齿动物模型中，分别使用仓鼠和大鼠作为供体和受体。下腔静脉，并结扎这些血管的近端，以端侧方式进行供体动脉和静脉的吻合。移植后立即切除受者腹主动脉和下腔静脉，对照组大鼠不使用免疫抑制剂，于 3.3±1 小时死亡。 0.5天(n=6)，DSG 5mg/kg/天治疗的大鼠死亡6.0±2.0 天（n=4），DSG 10mg/kg/天治疗的大鼠在 9.0±6.3 天（n=5）死亡。当严格分析时，两种 DSG 中的受体存活率。治疗组的移植物存活率在 10 mg/kd/day 的剂量下观察到最好，但有两只大鼠死亡。分别在第 3 天和第 5 天，在 10 mg/kg/天的治疗组中，这可能表明较高剂量的 DSG 对异种移植受者具有毒性作用，因此，我们以 5 mg/kg/天的剂量使用 DSG。兔肾移植实验模型中，对照组受者于第3、4、4、5天死亡，DSG治疗组受者于第4、4、4、5天死亡。这两种g之间没有显着差异。另一方面，在大鼠同种异体心脏移植模型中，我们在移植前的受者中免疫供者抗原，以扩增供者特异性淋巴细胞克隆，然后用DSG处理受者以消除这些特异性淋巴细胞克隆。克隆并诱导免疫无反应经证明，60％的接受者通过上述治疗获得了免疫无反应。我们现在将这种方法应用于啮齿动物。异种移植诱导肾受体的长期存活。