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目的探讨同种异基因骨髓移植小鼠急性移植物抗宿主病(aGVHD)模型的建立。方法将小鼠分为单纯照射组(A组)、同基因移植组(B组)、异基因移植组(C组),观察三组小鼠的造血重建、aGVHD的发生。结果 B组和C组WBC>1.0×109/L的时间分别为9.33±2.31d、10.33±1.65d(P=0.501);三组小鼠照射后前6d变化类似:体重进行性下降,伴活动减少,嗜睡,皱毛,弓背但无腹泻。A组小鼠于第6d开始死亡,死亡高峰在移植后9～12d,第12d全部死亡;B组小鼠第7d起体重逐渐增加,至移植后3w时体重恢复正常并继续增加,该组小鼠未出现aGVHD的症状,全部存活时间>60d;C组小鼠第7～10d体重略回升,11d后体重再度开始下降,并在11d左右再次出现活动减少,嗜睡,弓背,脱毛,腹泻等典型的aGVHD表现,死亡高峰在移植后第15～17d,第17d全部死亡,三组小鼠生存时间存在显著性差异(P<0.01)。对各组小鼠的肝脏、脾脏标本作常规病理切片结果显示:三组小鼠肝脏、脾脏第3d、第7d未见病变,单纯照射组小鼠第12d(濒死前)肝脏病变:肝脏部分肝细胞轻度水肿,出现空泡;脾脏髓质脾小体明显消失,大量红细胞坏死,含铁血黄素沉积。同基因骨髓移植组小鼠肝脏第14d病理学检查未见异常;脾脏可见脾小体缩小,髓质淋巴细胞未减少,纤维组织增生。异基因骨髓移植组小鼠第14d(发生aGVHD后3d)肝脏病变:肝脏出现肝细胞点状坏死,嗜酸性变,汇管区淋巴细胞浸润;脾脏髓质脾小体消失,脾窦扩张、瘀血、纤维组织增生,组织细胞增生典型;单纯照射组小鼠照射后6～12d全部死亡,同基因移植组小鼠全部长期生存,无GVHD征象,异基因移植组小鼠出现aGVHD征象;aGVHD的发病率为100%。结论 C57BL/6→BALB/C作为MHC不相合异基因移植动物模型,具有重复性好,发病率高,aGVHD表现典型,可作为aGVHD研究的理想参照。
Objective To investigate the establishment of acute graft-versus-host disease (aGVHD) model in allogeneic bone marrow transplantation mice. Methods The mice were divided into three groups: group A, group B and group C respectively. The hematopoietic reconstitution and aGVHD were observed in three groups of mice. Results The WBC> 1.0 × 109 / L in group B and group C were 9.33 ± 2.31 days and 10.33 ± 1.65 days respectively (P = 0.501). The changes in the first 6 days after irradiation in the three groups were similar: the weight decreased progressively with activity Reduce, drowsiness, wrinkly hair, bow back but no diarrhea. The mice in group A died on the 6th day and the peak of death died on the 9th to 12th day and the 12th day after transplantation. The weight of the mice in group B increased gradually from the 7th day to the 3rd week after transplantation, The mice were not aGVHD symptoms, all survival time> 60d; Group C mice 7th to 10d body weight rose slightly after 11d weight again began to decline, and again in about 11d activity decreased, drowsiness, bow, hair removal, diarrhea, etc. Typical aGVHD performance, the peak of death at 15 ~ 17d after transplantation, the first 17d all died, the survival time of three groups of mice significant difference (P <0.01). The routine histopathological examination of the liver and spleen of each group of mice showed that the liver and spleen of the three groups had no pathological changes on the 3rd and 7th days. The pathological changes of the liver Hepatocellular mild edema, there vacuolar; spleen and medulla spleen body was significantly disappeared, a large number of erythrocyte necrosis, hemosiderin deposition. On the 14th day, pathological examination of the liver of mice in the same gene bone marrow transplantation group showed no abnormalities. The spleen showed a narrowing of the spleen, no decrease of the medullary lymphocytes, and a proliferation of fibrous tissue. Allogeneic bone marrow transplantation group mice on the 14th day (3 days after aGVHD) liver lesions: liver hepatocyte punctate necrosis, eosinophilia, portal lymphocyte infiltration; splenic medullary spleen disappeared, splenic sinus dilation, blood stasis , Fibroblast hyperplasia and histiocytic hyperplasia. The mice in the irradiation group all died 6 to 12 days after irradiation. All the mice in the same gene transplantation group survived for a long time without GVHD. Allograft mice showed signs of aGVHD. The incidence of aGVHD The rate is 100%. Conclusion C57BL / 6 → BALB / C is an animal model of MHC mismatch allograft with good reproducibility, high incidence and typical aGVHD, which can be used as an ideal reference for aGVHD study.