| Co-Investigator(Kenkyū-buntansha) |
KENMOCHI Takashi National Cardiovascular Center, Department of Surgical Research, Researcher, 実験治療開発部, 研究員 (50215133)
HAYASHI Ryosuke National Cardiovascular Center, Department of Surgical Research, Chief Researche, 実験治療開発部, 室長 (00173047)
AMEMIYA Hiroshi National Cardiovascular Center, Department of Surgical Research, Director, 実験治療開発部, 部長 (80009563)
|
|---|
| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1989: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Research Abstract |
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 g
On 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
|
