T-bet、GATA-3及Th1/Th2在新型重型再生障碍性贫血模型小鼠外周血中的变化  

The expression of T-bet,GATA-3 and Th1 /Th2 in the peripheral blood of the novel severe aplastic anemia mouse model

作　　者：于晓棠[1] 徐瑞容[1] 林赠华[1] 刘红[1] 刘海燕[1] 陆雯萍 张晓丽[1] 陆伟[1] 

机构地区：[1]南通大学附属医院血液内科,江苏南通226001

出　　处：《广东医学》2013年第21期3230-3233,共4页Guangdong Medical Journal

基　　金：国家自然科学基金资助项目(编号:81070400);江苏省中医药局科技项目(编号:LZ11096);江苏省南通市科技计划社会发展项目(编号:S2010023)

摘　　要：目的通过测定γ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-γ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mRNA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-γ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。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.

关 键 词：再生障碍性贫血 动物模型 TH1 TH2 T—bet GATA-3 Foxp3 TNF-α 

分 类 号：R556.5[医药卫生—血液循环系统疾病]