摘要
目的通过检测IFN-γ干预博来霉素诱导大鼠肺纤维化时各组转录因子T-bet/GATA3 mRNA表达的变化,从而探讨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)、博来霉素致伤组(BLM1、BLM2、BLM4)及博来霉素+IFN-γ治疗组(BLM-IFN1、BLM-IFN2、BLM-IFN4)。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转录因子T-bet/GATA3 mRNA的表达。结果 BLM1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。半定量RT-PCR法显示各博莱霉素致伤组大鼠T-bet基因的表达均低于C组而GATA3基因的表达则高于C组(P均<0.01),IFN-γ干预后,BLM+INF1、BLM+INF2及BLM+INF4 3组T-bet基因的表达增加,与同时点的博来霉素致伤组对比均有显著性差异,GATA3基因表达在2周后显著减少,甚至低于C组。结论 IFN-γ干预能减轻博来霉素所致的肺纤维化作用,其机制可能与逆转了T-bet/GATA3失衡有关。
Objective To investigate the effects of IFN -γ on the expression of transcription factors T - bet/GATA3 mRNA in rat pulmonary fibrosis and thus to explore the potential therapeutic mechanism of IFN - γ on 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 （15mg/kg ×10day）. 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 T- bet/GATA3 in each group were measured with RT - PCR. Results 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. As compared with group C,the expression of T - bet gene was significantly lower in each bleomyein group,while GATA3 was remarkably higher. After treating with the IFN - γ, the expression of T - bet gene was significantly higher in BLM ＋ INF1 ,BLM ＋ INF2 and BLM ＋ INF4 than that in counterpart group of BLMs. The expression of GATA3 was remarkably decreased after two weeks, even lower than that in group C. Conclusion IFN - γ could alleviate the degree of rat pulmonary fibrosis induced by bloemycin. The mechanism might be related to that IFN - γ could reverse the out - of - balance of T - bet/GATA3.
出处
《医学研究杂志》
2013年第1期86-89,共4页
Journal of Medical Research
基金
浙江省金华市科技局技术创新基金资助项目(2006-3-008)
