转化生长因子β1对高体积分数氧暴露早产新生大鼠肺纤维化的调控作用(英文)  

Regulatory Role of Transforming Growth Factor β1 in Pulmonary Fibrosis in Hyperoxia-Exposed Premature Newborn Rats

作　　者：周晓光[1] 刘秀香[2] 刘仁红 肖昕[4] 常立文[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院儿科,武汉430030 [2]暨南大学附属第一医院儿科,广州510632 [3]深圳市宝安区沙井人民医院儿科,广东深圳518104 [4]中山大学附属第六医院儿科,广州510632

出　　处：《实用儿科临床杂志》2008年第14期1131-1135,共5页Journal of Applied Clinical Pediatrics

基　　金：National Natual Science Foundation of China(30672261,30770944)

摘　　要：目的探讨转化生长因子(TGF-β1)对高体积分数氧(高氧)暴露早产新生大鼠肺纤维化的调控作用。方法将80只早产新生SD大鼠随机分为空气组和高氧组,每组40只;每组又随机分为3、7、14、21d4个亚组。采用原位杂交法检测各亚组早产大鼠肺组织TGF-β1 mRNA表达与分布;采用免疫组织化学法检测各亚组早产大鼠肺组织TGF-β1蛋白、Ⅰ型与Ⅲ型胶原表达与分布;并用图像分析方法检测各亚组早产大鼠肺组织TGF-β1 mRNA及其蛋白与Ⅰ型、Ⅲ型胶原阳性表达的PU值。结果高氧第3天,肺组织TGF-β1 mRNA及其蛋白呈现弱阳性表达,第7、14、21天呈强阳性表达,其表达量于第7天开始增高,第14天达高峰;肺组织TGF-β1 mRNA及其蛋白阳性表达的PU值在第7、14、21天均高于空气组(Pa<0.01)。Ⅰ型胶原在第3、7天时呈弱阳性表达,第14、21天时呈强阳性表达,其表达量从第14天开始增加,第21天时达高峰;Ⅲ型胶原表达强度在第3天时呈弱阳性,第7天时开始增强呈中等阳性表达,第14、21天时呈强阳性表达,其表达量在第7天时开始增加,第14天时达高峰,表达量高于Ⅰ型胶原;肺组织Ⅰ型、Ⅲ型胶原阳性表达的PU值在第14、21天时均明显高于空气组(Pa<0.01)。高氧组肺组织TGF-β1 mRNA及其蛋白与Ⅰ型、Ⅲ型胶原阳性表达均分布于支气管和血管周围结缔组织及肺间质中;在第14、21天高氧组肺组织TGF-β1蛋白表达与Ⅰ型胶原呈显著正相关(r=0.881,0.793 Pa<0.01),与Ⅲ型胶原亦呈显著正相关(r=0.866,0.891 Pa<0.01)。结论TGF-β1过度表达而介导的细胞外基质(ECM)过度合成是肺纤维化发生的重要机制,在肺纤维化形成过程中TGF-β1对Ⅰ型、Ⅲ型胶原等ECM的沉积发挥重要的调控作用。Objective To explore the regulatory role of transforming growth factor β1（ TGF - β1） in pulmonary fibrosis in hypemxia - exposed premature newborn rats. Methods Eighty premature newborn Sprague - Dawley rats （ gestational age = 21 d） were randomly assigned into air group and hyperoxia group （40 each）. Each group was randomly divided into 4 subgroups ：3 d,7 d, 14 d and 21 d group. Expression and distribution of TGF - β1 mRNA in lung tissue of premature rats in these subgroups were detected by in situ hybridization. Immunohistochemical methods were applied to detect expression and distribution of TGF -β1 protein, type Ⅰ and type Ⅲ collagens in lung tissue of premature rats from various subgroups. Image analy- sis was used to measure positive unit（PU） values of positively expressed TGF- β1 mRNA and protein, type Ⅰ and type Ⅲ collagens in lung tissue. Results In hyperoxia group, expression of TGF - β1 mRNA and protein in lung tissue was weakly positive on day 3, strongly positive on day 7,14 and 21. The expression level began to increase from day 7 and reached a peak on day 14. PU values of positively expressed TGF -β1 mRNA and protein in lung tissue on day 7 ,14 and 21 were higher than those in air group（Pa 〈0.01 ）. Expression of type Ⅰ collagen was weakly positive on day 3 and 7, strongly positive on day 14 and 21. The expression level began to increase from day 14 and hit a high point on day 21. Expression of type Ⅲ collagen on day 3 was weakly positive,moderately positive on day 7 and strongly positive on day 14 and 21. The expression level began to rise on day 7 and pea- ked on day 14 and it was higher than that of type Ⅰ collagen. The PU values of positively expressed type Ⅰ and type Ⅲ collagens in lung tissue were significantly higher than those in air group（Pa 〈0.01 ）. In hyperoxia group,TGF - β1 mRNA,protein and type I and type Ⅲ collagens were positively expressed in bronchi,perivascular connective tissue and pulmonary interstitial. On day 14 and 21,

关 键 词：转化生长因子Β1 细胞外基质 高体积分数氧 肺纤维化 大鼠 早产 

分 类 号：R722.6[医药卫生—儿科]