CAJ | 학술논문

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.
목적 탐토골형태발생단백7(bone morphogenetic protein-7,BMP-7)대폐섬유화대서폐조직염증、섬유화정도급전화생장인자β1 (transforming growth factor-β1,TGF-β1)표체적영향.방법 장웅성Wister대서48지수궤분위정상대조조、섬유화조、소제량조화대제량조,매조12지.기관내관주박래매소A5제작폐섬유화모형.대소제량조화대제량조동물,매천분별이100 μg/kg、500 μg/kg제량복강주사BMP-7.각조재제작모형후제14、28천수궤처사6지대서.HE、Masson염색관찰폐조직병리변화,측정조직효원함량,면역조직화학측정폐조직중Ⅰ형효원단백급TGF-β1적표체,반정량반전록취합매련반응(RT-PCR)법측정폐조직TGF-β1 mRNA적표체.결과 BMP-7처리후제14、28천폐조직염증급섬유화정도균저우섬유화조,차이유통계학의의(P＜0.05).BMP-7사14 d、28 d시폐조직효원함량교동기섬유화조효원함량감소(P＜0.05).경과BMP-7처리,14 d、28 d시폐조직Ⅰ형효원화TGF-β1단백적표체균교섬유화조감약(P＜0.05).BMP-7사폐조직TGF-β1 mRNA적표체수평교동기섬유화조강저(P＜0.05).이차BMP-7적상술작용재대제량시경명현(P＜0.05).결론 재박래매소A5유도적대서폐섬유화모형중,BMP-7가이제량의뢰적방식억제폐조직염증급섬유화정도,기가능궤제가능여BMP-7억제TGF-β1재폐조직적표체유관.
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 the expression of TGF-β1 in lung tissue.