骨形态发生蛋白7对肺纤维化大鼠胶原和转化生长因子β1表达的影响  

Effect of bone morphogenetic protein-7 on the expression of collagen and transforming growth factor-1 in pulmonary fibrosis rats

作　　者：陈昊[1] 赵力[1] 丁芹[2] 陈碧[1] 罗涛[1] 李斯南[1] 

机构地区：[1]徐州医学院附属医院呼吸内科,221002 [2]徐州医学院附属医院感染性疾病科,221002

出　　处：《国际呼吸杂志》2013年第17期1308-1313,F0003,共7页International Journal of Respiration

基　　金：徐州市科技发展基金计划项目（XZZD1061）

摘　　要：目的 探讨骨形态发生蛋白7（bone morphogenetic protein-7,BMP-7）对肺纤维化大鼠肺组织炎症、纤维化程度及转化生长因子β1 （transforming growth factor-β1,TGF-β1）表达的影响.方法 将雄性Wister大鼠48只随机分为正常对照组、纤维化组、小剂量组和大剂量组,每组12只.气管内灌注博莱霉素A5制作肺纤维化模型.对小剂量组和大剂量组动物,每天分别以100 μg/kg、500 μg/kg剂量腹腔注射BMP-7.各组在制作模型后第14、28天随机处死6只大鼠.HE、Masson染色观察肺组织病理变化,测定组织胶原含量,免疫组织化学测定肺组织中Ⅰ型胶原蛋白及TGF-β1的表达,半定量反转录聚合酶链反应（RT-PCR）法测定肺组织TGF-β1 mRNA的表达.结果 BMP-7处理后第14、28天肺组织炎症及纤维化程度均低于纤维化组,差异有统计学意义（P＜0.05）.BMP-7使14 d、28 d时肺组织胶原含量较同期纤维化组胶原含量减少（P＜0.05）.经过BMP-7处理,14 d、28 d时肺组织Ⅰ型胶原和TGF-β1蛋白的表达均较纤维化组减弱（P＜0.05）.BMP-7使肺组织TGF-β1 mRNA的表达水平较同期纤维化组降低（P＜0.05）.而且BMP-7的上述作用在大剂量时更明显（P＜0.05）.结论 在博莱霉素A5诱导的大鼠肺纤维化模型中,BMP-7可以剂量依赖的方式抑制肺组织炎症及纤维化程度,其可能机制可能与BMP-7抑制TGF-β1在肺组织的表达有关.Objective To study the effects of bone morphogenetic protein 7 （BMP-7） on the expressions of collagen and transforming growth factor-β1 （TGF-β1） in lung tissues of rats with pulmonary fibrosis.Methods Forty-eight male Wistar rats were randomly divided into four groups with 12 rats in each group：the normal control group,the fibrosis group,the low-dose group,and the high-dose group.Pulmonary fibrosis was induced by intra-bronchial injection of bleomycin A5.Rats in low-dose group and high-dose group were intra-peritoneal injection of BMP-7 with dosages of 100 μtg/kg,500 μtg/kg once daily,respectively.Six rats in each group were sacrificed randomly on the 14 th and 28 th day after bleomycin A5 administration.The histological changes of lung tissue were evaluated by HE and Masson＇ s trichome stains.The level of tissue hydroxyproline was measured.The type Ⅰ collagen and TGF-β1 protein expressions were analyzed by immunohistochemistry.The TGF-β1 mRNA expression was detected by the semi-quantitative reverse transcription polymerase chain reaction （RT-PCR）.Results When treated with BMP-7,pulmonary inflammation and fibrosis were significantly reduced respectively as compared with the fibrosis group on the 14th and 28th day （P ＜0.05）.Compared with fibrosis group,BMP-7 could decrease the level of tissue hydroxyproline both on 14th and 28th day （P ＜0.05）.And after BMP-7 treatment,the expressions of type Ⅰ collagen and TGF-β1 protein,both on 14th and 28th day,were significantly decreased than that in fibrosis group （P ＜0.05）.Also,the TGF-β1 mRNA expression,on 14th and 28th day after BMP-7 treatment,was significantly decreased than that in fibrosis group （P ＜0.05）.Above effects of BMP-7 were more obvious in high-dose group than in low-dose group （P ＜ 0.05）.Conclusions BMP-7 could suppress bleomycin A5-induced rat pulmonary inflammation and fibrosis in dose-depended manner,with the possible mechanism of inhibiting the deposition of type Ⅰ collagen protein and decreasing

关 键 词：骨形态发生蛋白7 肺纤维化 转化生长因子Β1 胶原 

分 类 号：R563.9[医药卫生—呼吸系统]