供体骨髓细胞促进大鼠心脏移植耐受及机制的研究

经门静脉给予受体LEW大鼠3×10~8个DA大鼠供体脾细胞,2d后腹腔注射80mg/kg的环磷酰胺,第4天由舌静脉输注1×10~8骨髓细胞。2周后实施心脏移植手术。观察、记录移植物的存活时间,通过过继性转移实验,MLR、CTL活性测定及嵌合体分析,探讨耐受机制。结果表明,异基因心脏移植物的存活时间进一步延长;该耐受状态可被过继性转移;MLR、CTL活性表明,受体大鼠的免疫应答被特异性抑制;嵌合体水平提高。结论:异基因骨髓细胞输注可加深由脾细胞和环磷酰胺诱导的大鼠心脏移植耐受,该耐受与嵌合体水平、抑制细胞的存在有关。输注骨髓细胞对于改善、维持耐受状态,延长大鼠心脏移植物存活时间是一有效的方法。

Enhancement of Heart Transplantation Tolerance Induced with Cyclophosphamide by Infusion of Bone Marrow Cells in Rats

The heart transplantation tolerance was induced in rats by infusion of spleen cells through portal vein and ad-ministration of cyclophosamide by the intraperitoneal route; the bone marrow cells were infused by the glossal vein to in-crease the level of chimerism and to enhance the degree of tolerance induced, as vvell as to prolong the survival time of the cardiac allografts. Recipient LEW rats were infused with 3 x 10 allogeneic spleen cells of the donor DA rats by portal vein, and cyclophophamide was injected intraperitoneally in a dosage of 80 mg/kg 2 days later. On the 4th day , the bone marrow cells of the DA rats were infused to LEW rats by glossal vein. The heart grafting was carried out 2 weeks later , and the survival time of the grafts was observed and monitored. MLR, CTL activity, analysis of chimerism and adop-tive transfer tests were used to investigate the mechanism of tolerance. The experimental results showed that the survival time of the cardiac allografts was significantly prolonged, and the immune responses of the recipient rats were inhibited in donor-specific manner as demonstrated by MLR and CTL release activities. The stable mixed chimerism could be detected in thymus and peripheral blood, and the tolerant state could be adoptively transferred in vivo. It concludes that the infusion of bone marrow cells can enhance the tolerance induced by spleen cells plus cyclophosphamide protocol, and this tolerance may be associated with the levels of chimerism and the presence of suppressor cells. infusion of the bone marrow cells might be an effective method for ameliorating and maintaining the tolerant state and for the prolongation of survival time of the cardiac allografts.