【摘要】 目的探讨门静脉输注供者的凋亡骨髓细胞对大鼠移植心脏存活时间的影响。方法以Wistar大鼠为供者、SD大鼠为受者,将其随机分为4组,每组15只,A组为对照组,受者术前6d经门静脉输注RPMI1640培养基0.5ml,术后不注射环孢素A(CsA);B组为骨髓细胞输注组,受者术前6d经门静脉输注供者的骨髓细胞5×107个,术后不用CsA;C组为凋亡细胞输注组,受者术前6d经门静脉输注供者的凋亡骨髓细胞5×107个,术后不用CsA;D组为CsA组,受者术前3d起腹腔注射CsA5mg/kg,直至术后10d。60Coγ射线照射诱导骨髓细胞凋亡,各组大鼠建立腹部异位心脏移植模型。观察各组移植心的存活时间、组织病理学改变,测定受者血清中白细胞介素10(IL-10)及转化生长因子β1(TGF-β1)的含量及单向混合淋巴细胞培养(MLR)结果。结果C组移植心的存活时间为(14.00±0.95)d,较A组明显延长(P<0.01),但仍未达到长期存活(存活时间短于CsA组)。术后7d,C组移植心组织切片呈现中度急性排斥反应,心肌细胞损害不明显,但有大量淋巴细胞浸润。除术后7d的TGF-β1外,C组其它各测定时点的血清IL-10及TGF-β1均高于其它3个组。C组大鼠的脾细胞在供鼠脾细胞的刺激下,细胞增殖反应明显低于A组、B组(P<0.01),而对第三品系大鼠的脾细胞仍有较强的增殖反应,具有明显的抗原特异性;CsA组的细胞增殖均被抑制。结论门静脉预输注供者的凋亡骨髓细胞,可明显延长大鼠移植心脏的存活时间,但单纯单剂量的输注凋亡细胞并不足以建立长期、稳定的免疫耐受。更多还原

【Abstract】 Objective To study the effects of administration of donor apoptotic bone marrow cells via portal vein on the survival time of heart transplantation in rats.Methods Wistar rats were selected as donors and SD rats as recipients, and divided into 4 groups at random. In groups A, B and C, the animals were injected via portal vein with RPMI 1640 0.5 ml 6 as control group, 5×107 donor bone marrow cells and 5×107 apoptotic donor bone marrow cells 6 days before transplantation, respectively , and not subjected to cyclosporin A （CsA）. In group D, the animals were injected intra- peritoneally with CsA 5 mg/kg from 3 days before transplantation till 10 days post operation. Bone marrow cells apoptosis was induced by 60 Coγ radiation. Heart transplantation models were established in each group. The survival time of donor heart and histological changes were observed. Serum concentrations of IL-10 and TGF-β₁ of recipients and mixed lymphocyte reaction （MLR） were measured. Results The survival time of heart allografts in the group C （ 14.00 ± 0.95 ） was significantly longer than in group A （P< 0.01 ）, but couldn’t maintain long-term survival （shorter than group D）. Histological changed showed mid-degree acute rejection in group C, the injury of myocardium was not significant but there were plenty of lymphocytes infiltration. The serum concentrations of IL-10 and TGF-β₁ in group C were significantly higher than other groups except the TGF-β₁ at 7th day after operations . With the stimulation of donor spleen cells, the proliferation reaction in group C was lower than in groups A and B （P< 0.01 ）, while maintained normal reaction with the stimulation of the third strain rat spleen cells, that showed an antigen specific character.Conclusions Administration of donor apoptotic cells via portal vein before allogenic heart transplantation can prolong the survival time of donor hearts, but simple and one dose infusion of apoptotic cells is not enough to establish a stable and long-time tolerance.更多还原