三氧化二砷对转化生长因子β_1诱导的大鼠肺成纤维细胞增殖的影响  

Effects of arsenic trioxide on proliferation of pulmonary fibroblasts induced by transforming growth factor-β_1 in rats

作　　者：盖磊[1] 李惠萍[2] 

机构地区：[1]苏州大学医学院,江苏苏州215000 [2]同济大学附属上海市肺科医院呼吸科,上海200433

出　　处：《临床荟萃》2013年第7期769-771,779,F0002,共5页Clinical Focus

基　　金：国家自然科学基金资助项目(30671996);上海市科委科研基金资助项目(09411951500)

摘　　要：目的探讨三氧化二砷(arsenic trioxide,As2O3)对转化生长因子β1(transforming growth factor-β1,TGF-β1)诱导的成纤维细胞增殖的影响。方法实验采用分离培养正常健康SD大鼠肺组织的成纤维细胞。取对数生长期的细胞随机分为空白组(正常成纤维细胞)、模型组(加入0.5μg/L浓度的TGF-β1的成纤维细胞)、以及干预组(在TGF-β1诱导的成纤维细胞中分别加入浓度为0.5、1、2μmol/L的As2O3),取12、24、48小时为观察时间点。用活细胞动态分析系统(Cell-IQ)观察各组细胞的形态和生长情况。用四甲基偶氮唑蓝(MTT)方法观察各组细胞的增殖抑制率。结果不同浓度As2O3干预组中大鼠肺成纤维细胞的增殖均受到抑制,抑制程度具有明显的剂量—时间依赖性,细胞增殖抑制率以各浓度As2O3干预组48小时观察时间点和2μmol/L干预组最为明显(P<0.01)。不同浓度As2O3干预组在48小时观察时间点的细胞增殖抑制率分别为(14.76±2.16)%、(32.55±2.80)%、(57.41±3.25)%(均P<0.01);2μmol/L干预组12小时、24小时、48小时的细胞增殖抑制率分别为(30.53±2.38)%、(41.29±2.67%)%、(57.41±3.25)%(均P<0.01),并且分别与0.5μmol/L及1μmol/L干预组在这3个时间点的细胞增殖抑制率相比,差异均有统计学意义(P<0.01)。结论 As2O3能抑制TGF-β1诱导的大鼠肺成纤维细胞增殖,从而可能起到减轻肺纤维化的作用。Objective To investigate the effects of arsenic trioxide（As2O3） on pulmonary fibroblasts induced by transforming growth factor-β1 （TGF-β1）. Methods The experiment utilized isolated and cultured pulmonary fibrohlasts from healthy SD rats, fibroblasts in logarithmic phase were randomly divided into blank group（normal fibroblasts）, model group（added 5 μg/L TGF-β1 in normal fibroblasts）and intervention groups （added 0.5,1,2 μmol/L As2O3 in fibroblasts induced by TGF-β1 ）,all groups were observed on 12 h,24 h,48 h. The morphology and growth of cells in each group were observed by live-cell imaging and analysis platform （Cell-IQ）. The inhibition rate of fibroblasts proliferation was detected by MTT assay. Results Various concentrations of As203 significantly inhibited the proliferation of the fibroblasts in intervention groups, and showed a dose-dependent and time-dependent tendency. The inhibition rate of intervention groups at 48 h and As2 O3 concentration as 2 μmol/L was significantly higher than that of other groups （ P 〈0.01）. The inhibition rate of various concentrations of As303 at 48 h was respectively （14.76± 2.16）%, （32.55 ± 2.80 ） %, （57.41±3.25 ） % （all P〈 0.01 ）;the inhibition rate of As2 03 concentration 2 μmol/L intervention group for 12 h,24 h,48 h was respectively（30.53±2.38） %,（41. 29±2.67） %,（57.41±3. 25）%（allP 0.01） ,and the inhibition rate in the three time points showed significant difference compared with As2 03 concentration 0.5 μmol/L and 1 μmol/L intervention groups （all P〈0.01）. Conclusion As2O3 can inhibit the proliferation of fibroblasts induced by TGF-β1 ,it may play an effect as antifibrosis in lungs.

关 键 词：肺纤维化 转化生长因子Β 三氧化二砷 成纤维细胞 

分 类 号：R563[医药卫生—呼吸系统]