中文摘要：

目的通过测定叮干扰素（IFN-γ）联合白消安诱导的新型重型再生障碍性贫血（AA）模型小鼠外周血单个核细胞Th1／Th2比例及T—bet、GATA-3等细胞因子的表达情况，进一步论证该模型小鼠的免疫学合理性。方法应用IFN-γ腹腔注射联合白消安灌胃诱导建立BALB／c小鼠重型AA模型（联合组，n=10），以白消安灌胃联合生理盐水腹腔注射处理的为白消安组（n=10）、生理盐水灌胃联合IFN-γ腹腔注射处理的为IFN-1组（n=10）和生理盐水灌胃联合生理盐水腹腔注射处理的为正常组（n=10）作对照，分别收集各组小鼠的外周血，采用流式细胞术检测Th1／Th2的比值，用RT—PCR技术检测各组小鼠外周血单个核细胞T—bet、GATA-3、Foxp3、TNF～α基因mRNA的表达情况。结果联合组小鼠外周血中Th1／Th2的比例、T—bet、TNF-α基因mR-NA的表达及T—bet／GATA的比率较其他各组显著升高，而GATA-3基因mRNA的表达则显著降低，差异有统计学意义（P〈0．05）。联合组小鼠外周血单个核细胞Foxp3基因mRNA的表达显著低于正常组和IFN-1组，但高于白消安组，差异有统计学意义（P〈0．05）。结论IFN-γ联合白消安诱导建立的新型重型AA小鼠Th1／Th2比例及T—bet／GATA-3比率变化与AA患者相同，提示该小鼠重型AA模型可能更符合人类免疫介导的骨髓造血功能损伤，可以为今后AA的研究提供新平台。

英文摘要：

Objective To evaluate the rationality of the interferon-γ （IFN -γ） combined busulphan- induced severe aplastic anemia （SAA） mouse model via analysis of the ratio of Thl/Th2, and the expression of cytokines T- bet and GATA - 3 in the peripheral blood mononuclear cells. Methods The BALB/c female mice were intraperitoneal injec- ted with IFN -γ and/or intragastric administrated with busulphan to set up the SAA model （associated group, n = 10） , busulphan group （n = 10） or IFN -γ group （n = 10） ; and a control group （n = 10） was also set up. The ratio of Thl/ Th2 and the mRNA expression of T - bet, GATA - 3, Foxp3 and TNF - α in peripheral blood were assessed by using flow cytometry and RT - PCR, respectively. Results The Th1/Th2, T - bet/GATA and the mRNA expression of T - bet and TNF -α were significantly increased, whereas the mRNA expression of GATA - 3 was reduced in the associated group, compared with other groups （ P 〈 0. 05 ）. The mRNA expression of Foxp3 gene in the peripheral blood mononuclear cells was significantly lower in associated group than normal group and IFN -γ group, but higher than busulphan group （ P 〈 0. 05）. Conclusion The change of Th1/Th2 proportion and T - bet/GATA ratio in the novel SAA mouse model induced by IFN - γ combined with busulphan were similar with AA patients, providing evidences of further study on AA in the future.