干扰素γ对大鼠肺纤维化转录因子GATA3的影响

Effects of IFN-γ on the expression of transcription factors GATA3 in rat pulmonary fibrosis

目的:探讨大鼠肺纤维化时转录因子GATA3 mRNA的表达,以及干扰素γ(IFN-γ)干预肺纤维化的机制。方法:腹腔注射博莱霉素(BLM)诱导大鼠肺纤维化动物模型。雄性SD大鼠随机均分为对照组(C组)、BLM组(BLM1、BLM2、BLM4分别为造模第1周、2周、4周)及BLM+IFN-γ组(BLM-IFN1、BLM-IFN2、BLM-IFN4分别为造模第1周、2周、4周)。对各组肺组织纤维化的程度行病理半定量评估,检测各组外周血单个核细胞(PMBC)转录因子GATA3 mRNA的表达。结果:①BLM1及BLM-IFN1组肺组织病理改变以肺泡炎为主,BLM2组兼有肺泡炎和纤维化病变,BLM4组以肺纤维化为主,BLM-INF2及BLM-INF4组中发现肺纤维化程度减轻。②半定量RT-PCR法显示各BLM组大鼠GATA3基因的表达则高于C组(均P<0.01),IFN-γ干预后,BLM-INF1、BLM-INF2及BLM-INF4三组GATA3基因表达减少,甚至低于C组。结论:IFN-γ干预能减轻BLM所致的肺纤维化作用,其机制可能与IFN-γ能抑制GATA3表达,逆转Th1/Th2失衡有关。

Objective： To explore the effects of IFN-γ on the expression of transcription factors GATA3 in rat pulmonary fibrosis. Methods： Male SD rats were randomly divided into three groups： the control group （C）, bloemycin groups （group BLM） and IFN-γ treated group （group BLM -IFN）. The pulmonary fibrosis model was established by intraperitoneal injection with bloemycin （15 mg/kg × 10 day）. Rats in BLM and BLM-IFN group were randomly sacrificed on 7th day （group BLM1 and BLM -IFN1）, 14th day （group BLM2 and BLM-IFN2） and 28th day （group BLM4 and BLM -IFN4）, respectively. Semi-quantitative analysis of the histopathologic changes stained with Haematoxylin-eosin （H-E） was performed, and the mRNA expression of transcription factors GATA3 in each group was measured with RT-PCR. Results： ① alveolitis was the primarily pathologic change of lung tissue in BLM1 and BLM-IFN1, while alveolitis and fibrosis in BLM2 and fibrosis in BLM4. Obviously alleviated fibrosis was seen in both BLM-IFN2 and BLM-IFN4 group. ② As compared with group C, the expression of GATA3 gene was significantly higher in each bleomycin group, （P〈0.01 respectively）. After treatment with IFN-γ, the expression of GATA3 gene in BLM-INF1, BLM-INF2 and BLM-INF4 was lower than that in counterpart group of BLMs. （P〈0.01 respectively）, even lower than that in group C. Conclusion： IFN-γ treatment can reduce the degree of rat pulmonary fibrosis induced by bloemycin. The mechanism may be that the IFN-γ can inhibit the expression of GATA3 gene, and reverse the imbalance of Thl/Th2.