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目的 :探讨克服异种骨髓移植间强烈的移植物抗宿主病的方法。方法 :实验分两步 :第一步 ,SD大鼠亚致死剂量 5 .5Gy全身照射后 ,4h内经尾静脉输入正常BALB/c小鼠骨髓细胞 8× 10 7。 2d后予腹腔注射Cy15 0mg/kg。诱导形成嵌合体大鼠 ,使其对BALB/c小鼠产生特异性免疫耐受。第二步 ,BALB/c小鼠接受致死剂量 9.0Gy全身照射 ,随机三分组。照射后 4h内经尾静脉注射骨髓进行移植。A组输注正常SD大鼠的骨髓细胞 4× 10 7;B组输注正常SD大鼠的骨髓细胞 4× 10 7和脾细胞 2× 10 7;C组输注嵌合体SD大鼠的骨髓细胞 4× 10 7和脾细胞 2× 10 7;比较GVHD发生情况。结果 :A组有 2只小鼠死于感染和放射损伤 ,所有对象均未观察到明显GVHD表现。B组平均存活时间为 (9.0± 1.3)d ,且死前均出现不同程度的典型GVHD表现 ,如皮毛脏乱、消瘦、弓背体位、腹泻 ,甚至血便等 ;肝实质内有灶性淋巴细胞及多形细胞浸润 ,并可见局灶性坏死 ;肠绒毛部分或大部分脱落 ,粘膜坏死、有大量炎性细胞浸润 ,符合GVHD病理改变。而C组除 2只小鼠分别于 18d、31d死亡外 ,余均存活超过 6 0d ,与B组有显著差异 ,且死亡率最低。结论 :有受者嵌合体的供者 ,在进行异种骨髓移植后有助于克服异种移植物抗宿主病。
Objective: To explore ways to overcome the strong graft-versus-host disease in heterogeneous bone marrow transplantation. Methods: The experiment was divided into two steps: In the first step, 8 × 10 7 cells of normal BALB / c mouse bone marrow cells were transplanted via the tail vein within 4 hours after sublethal dose of 5.5 Gy in SD rats. 2d after intraperitoneal injection of Cy15 0mg / kg. Chimera rats were induced to form specific immune tolerance to BALB / c mice. In the second step, BALB / c mice received a lethal dose of 9.0 Gy whole body irradiation and were randomly divided into three groups. Bone marrow was transplanted via caudal vein within 4 hours after irradiation. A group of normal SD rats infused bone marrow cells 4 × 10 7; B group infused normal SD rat bone marrow cells 4 × 10 7 and spleen cells 2 × 10 7; C group infused chimera SD rats bone marrow 4 × 10 7 cells and 2 × 10 7 spleen cells; compare the incidence of GVHD. RESULTS: Two mice in group A died of infection and radiation injury, and no significant GVHD was observed in all subjects. The mean survival time in group B was (9.0 ± 1.3) d, with typical GVHD manifestations before death, such as dirty skin, emaciation, bow and back position, diarrhea and bloody stools. There were focal lymphocytes And pleomorphic cell infiltration, and visible focal necrosis; part or most of intestinal villi shedding, mucosal necrosis, a large number of inflammatory cell infiltration, in line with the pathological changes of GVHD. The C group except two mice were died on the 18th and 31th days respectively, all survived more than 60 days, which was significantly different from that of the B group and the mortality was the lowest. CONCLUSIONS: Donors with recipient chimeras contribute to overcoming xenograft versus host disease after xenotransplantation of bone marrow.