^(137)Cs γ射线联合环磷酰胺与氯霉素介导的获得性再生障碍性贫血小鼠模型的建立

Establishment of ^(137)Cs γ ray Combined with Cyclophosphamide and Chloramphenicol-Mediated Mouse Model of Acquired Aplastic Anemia

目的:对γ射线(^(137)Cs)联合环磷酰胺与氯霉素介导的获得性再生障碍性贫血小鼠模型进行改进研究,为再生障碍性贫血发病机制和治疗的研究提供稳定模型。方法:BALB/c小鼠经3-5 Gy^(137)Csγ射线(91 cGy/min)照射后,于d 4、5、6腹腔注射环磷酰胺25 mg/(kg·d)、氯霉素62. 5 mg/(kg·d),观察其外周血白细胞计数、网织红细胞计数、骨髓涂片及骨髓有核细胞计数、骨髓病理切片等指标。结果:经^(137)Csγ射线照射联合环磷酰胺、氯霉素腹腔注射的BALB/c小鼠的外周血三系细胞均迅速减少,其中白细胞、血小板、网织红细胞表现得尤为明显;于d14降至最低,在d 28三系细胞仍然严重减少,骨髓有核细胞数量明显下降,骨髓增生程度呈减低或重度减低;骨髓病理切片示造血细胞重度减少;脂肪细胞等非造血细胞增多。结论:通过^(137)Csγ射线照射并联合环磷酰胺、氯霉素腹腔注射的小鼠模型,其各项检测指标均达到获得性再生障碍性贫血的诊断标准,可作为获得性再生障碍性贫血发病机制及治疗研究的小鼠模型。

Objective:To improve and establish the mouse model with aplastic anemia(AA)mediated by137 Cs γ-ray irradiation combined with cyclophosphamide(CTX)and chloramphenicol(CHL)injection,so as to provide a stable model for studying the pathogenesis and treatment of AA.Methods:The BALB/c mice were exposed to137 Cs γ-ray of3-5 Gy(91 cG y/min)and were intraperitoneally injected with CTX of 25 mg/(kg.d)and CHL of 62.5 mg/(kg.d)at D 4,5 and 6 after irradiation;the WBC,platelet and reticulocyte counts in peripheral blood as well as the mucleated cell count in bone marrow and bone marrow smears were detected.Results:The 3-lineage cells in peripheral blood of BALB/c mouse model with acquired AA were rapidly reduced,especially WBC,platelet and reticulocyte counts were low est at D 14,the 3-lineage cells in peripheral blood were still severely reduced at D 28;the nucleated cell count in bone marrow significantly dcreased,the bone marrow hyperplasia was reduced or severely reduced;the pathological sections of bone marrow showed the severe reduction of hematopoietic cells and the increased of non-hematopoietic cells such as fat cells.Conclusion:The mouse model with acquired AA has been established by137 Csγ-ray irradiation combined with CTX and CHL injection.All detection indicators of this model reach to diagnostic criteria for acquired AA,therefore this mouse model may be used as the model for study of pathogenesis and treatment of acquired AA.