目的探讨干扰素-γ(interferon-γ,IFN-γ)联合白消安诱导小鼠重型再生障碍性贫血(再障)模型的建立。方法随机选取30只清洁级BALB/c雌性小鼠,采用腹腔注射IFN-γ联合胃饲白消安的方法制作重型再障模型,以单纯白消安组(单M组)(n=30)和对照组(n=30)为对照,比较3组小鼠间一般情况、患病率、死亡率、血常规、胫骨骨髓有核细胞计数(tibial nucleated cell count,TNCC)、脾脏指数、骨髓细胞形态学及骨髓活组织病理学检查的结果。结果IFN-γ与白消安联合组(联合用药组):至给药结束后第10天,重型再障患病率达100%,死亡率为20%;联合用药组WBC、Hb、PLT、网织红细胞绝对值(Ret)、TNCC分别为(0.8±0.3)×10^9/L、(45±20)g/L、(10±8)×10^9/L、(15.2±10.2)×10^9/L、(12±7)×10^6/根胫骨,与单M组和对照组比较均有显著性差异(P〈0.05);至给药结束后第20天,WBC、Hb、PLT及TNCC与单M组和对照组比较仍有显著性差异(P〈0.05)。骨髓细胞形态学及骨髓活组织病理学检查示联合用药组骨髓增生极度低下,脂肪化明显,造血细胞减少,脂肪细胞和淋巴细胞等非造血细胞增加,骨髓抑制严重且不可逆;单M组外周血常规、TNCC及骨髓有核细胞增生均可随时间延长逐渐恢复,易见骨髓红系代偿性增生旺盛及病态造血现象。结论IFN-γ与白消安合用可在较短时间内诱导建立小鼠重型再障动物模型,方法简便,诱导成功率高,更接近于人类再障。
Objective To establish a novel severe aplastic anemia (SAA) mouse model by interferon-γ (IFN-γ) plus husulphan. Methods Thirty clean-class BALB/e female mice were intraperitoneally injected with IFN-γ and intragastrically administrated with busulphan( group Ⅰ ) , meanwhile busulphan alone group ( n = 30, group Ⅱ ) and normal control group ( n = 30, group Ⅲ ). Multi-parameters were compared among the three groups. Results In group Ⅰ at day 10 after treatment, the incidence of SAA was 100% and mortality 20% respectively ; the WBC, HGB, PLT, absolute reticuloeyte count (Ret) and tibial nucleated cell count (TNCC) were (0.8 ±0.3) × 10^9/L, (45 ±20) g/L, (10 ±8) × 10^9/L, (15.2 ± 10.2) × 10^9/ L, ( 12 ±7)× 10^6/tibia, respectively, which were significantly different from the other two groups ( all P 〈 0.05 ). The bone marrow smears and patho-histological examinations showed marked reductions of marrow cell proliferation, and increases of the percentages of non-hematopeitic cells and cellula adipose. The depression was severe and irreversible. In group Ⅱ , the blood cells count, TNCC and marrow proliferation recovered gradually with erythroid hyperplasia and hematopoietic dysplasia. Conclusions IFN-γ plus busulphan can establish a SAA mouse model in a relatively short period, which is more resemble with human SAA.