目的:建立一个稳定可靠的异基因骨髓移植(allogeneic bone marrow transplantation,Allo-BMT)急性移植物抗宿主病(acute graft-versus-host disease,aGVHD)动物模型,为Allo-BMT中aGVHD研究提供理想的实验平台。方法:以雄性C57BL/6(H-2b...目的:建立一个稳定可靠的异基因骨髓移植(allogeneic bone marrow transplantation,Allo-BMT)急性移植物抗宿主病(acute graft-versus-host disease,aGVHD)动物模型,为Allo-BMT中aGVHD研究提供理想的实验平台。方法:以雄性C57BL/6(H-2b)为供鼠,雌性BALB/C(H-2d)为受鼠,受鼠致死性全身照射(total body irradiation,TBI)(8.0Gy)预处理后,在移植物中混合不同比例的供鼠骨髓细胞和脾细胞以引起不同程度的aGVHD。根据存活期、外周血白细胞计数、临床表现及病理检查等判断aGVHD程度。结果:单纯异基因骨髓组只有部分小鼠出现aGVHD,75%的小鼠长期存活(>30d)。混合不同比例的供鼠骨髓细胞和脾细胞的Allo-BMT小鼠出现aGVHD的时间和程度均有差异,其中骨髓与脾细胞1.5:1或1:1混合组小鼠,均可在相对集中的时间内(8～15d)观察到典型的aGVHD临床和病理改变。结论:建立Allo-BMT aGVHD模型需要加入一定比例的脾细胞,供鼠骨髓与脾细胞1.5:1或1:1混合进行的Allo-BMT,可作为理想的aGVHD动物模型。展开更多
To explore the effect and pathogenssis of acute graft-versus-host disease (aGVHD) on early diffuse lung injury in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we established an aGVHD model of C57BL/...To explore the effect and pathogenssis of acute graft-versus-host disease (aGVHD) on early diffuse lung injury in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we established an aGVHD model of C57BL/6→BALB/c mice. Chest computed tomography (CT) scans, histopathology and the levels of cytokines including tumor necrosis factor α (TNFα) and Interferon (IFNγ) in lungs were dynamically detected in recipient mice after transplantation. The incidence of aGVHD was respectively 0%, 0% and 100% in simple irradiation group (A), syngeneic transplant group(B) and allogeneic transplant group (C). Chest CT scans of recipient mice were normal in 3 groups on days +3 and +7 after transplantation. CT showed that two of ten mice had bilateral lung diffuse infiltrate on day +12 (on the brink of death) in group A and 6 of 10 mice had bilateral lung diffuse infiltrate on day +14 (3 d after aGVHD occurring) in group C, and were normal on days +12 and +14 in group B after transplantation. Histopathology of lungs in the 3 groups was similar, consisting of minor interstitial pneumonitis on day +3. Group A showed edema, hyperplasia of epithelial cells and widened alveolar interval on day +7, and epithelial cell necrosis, lymphocyte infiltration, hemorrhage, protein leakage, and local consolidation on day +12. The histopathology of group B showed slight edema of epithelial cells on +7 day, which were slighter than that on day +3, and virtually normal on day +14. The histopathology in group C was characterized by the significant expansion and congestion of capillaries, and lymphocyte infiltration on day +7, the acute pneumonitis was present involving tissue edema, lymphocyte and macrophage infiltration, protein leakage and perivascular inflammation on day +14. In group A, the levels of TNFα were lower on day +7 than on day +3. In group B, the levels of TNFα attained a peak on day +3, which decreased on days +7 and +14. In group C, the levels of TNFα were highest on day +7 and there was a significant difference betwee展开更多
文摘目的:建立一个稳定可靠的异基因骨髓移植(allogeneic bone marrow transplantation,Allo-BMT)急性移植物抗宿主病(acute graft-versus-host disease,aGVHD)动物模型,为Allo-BMT中aGVHD研究提供理想的实验平台。方法:以雄性C57BL/6(H-2b)为供鼠,雌性BALB/C(H-2d)为受鼠,受鼠致死性全身照射(total body irradiation,TBI)(8.0Gy)预处理后,在移植物中混合不同比例的供鼠骨髓细胞和脾细胞以引起不同程度的aGVHD。根据存活期、外周血白细胞计数、临床表现及病理检查等判断aGVHD程度。结果:单纯异基因骨髓组只有部分小鼠出现aGVHD,75%的小鼠长期存活(>30d)。混合不同比例的供鼠骨髓细胞和脾细胞的Allo-BMT小鼠出现aGVHD的时间和程度均有差异,其中骨髓与脾细胞1.5:1或1:1混合组小鼠,均可在相对集中的时间内(8～15d)观察到典型的aGVHD临床和病理改变。结论:建立Allo-BMT aGVHD模型需要加入一定比例的脾细胞,供鼠骨髓与脾细胞1.5:1或1:1混合进行的Allo-BMT,可作为理想的aGVHD动物模型。
基金Supported by the National Natural Science Foundation of China (Grant No. 30971300)
文摘To explore the effect and pathogenssis of acute graft-versus-host disease (aGVHD) on early diffuse lung injury in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we established an aGVHD model of C57BL/6→BALB/c mice. Chest computed tomography (CT) scans, histopathology and the levels of cytokines including tumor necrosis factor α (TNFα) and Interferon (IFNγ) in lungs were dynamically detected in recipient mice after transplantation. The incidence of aGVHD was respectively 0%, 0% and 100% in simple irradiation group (A), syngeneic transplant group(B) and allogeneic transplant group (C). Chest CT scans of recipient mice were normal in 3 groups on days +3 and +7 after transplantation. CT showed that two of ten mice had bilateral lung diffuse infiltrate on day +12 (on the brink of death) in group A and 6 of 10 mice had bilateral lung diffuse infiltrate on day +14 (3 d after aGVHD occurring) in group C, and were normal on days +12 and +14 in group B after transplantation. Histopathology of lungs in the 3 groups was similar, consisting of minor interstitial pneumonitis on day +3. Group A showed edema, hyperplasia of epithelial cells and widened alveolar interval on day +7, and epithelial cell necrosis, lymphocyte infiltration, hemorrhage, protein leakage, and local consolidation on day +12. The histopathology of group B showed slight edema of epithelial cells on +7 day, which were slighter than that on day +3, and virtually normal on day +14. The histopathology in group C was characterized by the significant expansion and congestion of capillaries, and lymphocyte infiltration on day +7, the acute pneumonitis was present involving tissue edema, lymphocyte and macrophage infiltration, protein leakage and perivascular inflammation on day +14. In group A, the levels of TNFα were lower on day +7 than on day +3. In group B, the levels of TNFα attained a peak on day +3, which decreased on days +7 and +14. In group C, the levels of TNFα were highest on day +7 and there was a significant difference betwee
