摘要
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:This experiment is in order to prevent xenogeneic graft-versus-host disease (XGVHD) in xenogeneic bone marrow transplantation.Methods:The experiment includes two procedure. First, SD rats were conditioned with 5.5Gy sublethal total body irradiation(TBI), followed in 4hours by infusion of 8×10 7 BALB/c mice bone marrow cells on day 0 , then it were intraperitonially administered 150mg/kg cyclophosphamide (cp) on day 2 . The procedure let SD rats become chimerism and have specific immunologic tolerance. Second, BALB/c mice were conditioned with 9.0Gy lethal TBI and divided into three groups randomly. Group A were injected with bone marrow cells 4×10 7 from normal rats, and group B were injected with bone marrow cells 4×10 7 and speen cells 2×10 7 from normal rats, and group C were injected with bone marrow cells 4×10 7 and speen cells 2×10 7 from chimeric rats. Then they were observed about GVHD for 60 days.Results: In the second experiment,two mice of group A were died because of infection respectively, and they weren't observed for GVHD.Mice of group B appeared with variant degree of wasting, diarrhea, fur losing, arched b body posture, even appeared loody stool, and all of all died within 8~15 days, so its living average 9.0±1.3days. Pathologic changes of liver and intestine were inflaming cells infiltrating and necrotizing. Mice of group C mostly survived for more than 60 days, but two mice died respectively on day 18,31 after transplanting. Surviving time of group B compared with group C were significant.Conclusion:Using chimeric donors can prevent XGVHD in xenogeneic bone marrow transplantation.
出处
《中国现代医学杂志》
CAS
CSCD
2003年第13期1-4,共4页
China Journal of Modern Medicine
关键词
嵌合体
移植物抗宿主病
骨髓移植
异种
Chimerism
Graft-Versus-Host Disease
Bone Marrow Transplantation
Xenogeneic