文章摘要
李冰洁,李淑君,罗妍妍,卢红艳,陈筱青,吴升华.脂氧素A4调控转化生长因子-β1干预小鼠支气管肺发育不良的机制研究[J].南京医科大学学报,2016,(11):1326~1332
脂氧素A4调控转化生长因子-β1干预小鼠支气管肺发育不良的机制研究
Mechanisms of lipoxin A4 attenuating bronchopulmonary dysplasia via regulation of TGF-β1
投稿时间:2016-03-18  
DOI:10.7655/NYDXBNS20161109
中文关键词: 脂氧素A4  转化生长因子-β1  支气管肺发育不良
英文关键词: lipoxin A4  transforming growth factor-β1  bronchopulmonary dysplasia
基金项目:
作者单位
李冰洁 南京医科大学第一附属医院儿科,江苏 南京 210029 
李淑君 南京医科大学第一附属医院儿科,江苏 南京 210029 
罗妍妍 南京医科大学第一附属医院儿科,江苏 南京 210029 
卢红艳 江苏大学附属医院儿科,江苏 镇江 212001 
陈筱青 南京医科大学第一附属医院儿科,江苏 南京 210029 
吴升华 南京医科大学第一附属医院儿科,江苏 南京 210029 
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中文摘要:
      探讨脂氧素A4(lipoxin A4,LXA4)对新生小鼠高氧诱导所致的支气管发育不良(bronchopulmonary dysplasia,BPD)的保护作用及可能机制?方法:利用高氧损伤诱导BPD动物模型,将新生C57BL/6J小鼠随机分成:空气对照组?模型组?LXA4干预组?转化生长因子-β1(transforming growth factor-β1,TGF-β1)中和抗体(1D11)干预组,记录仔鼠体重和生存情况,HE染色观察出生后肺组织病理改变,qPCR法检测肺纤维化指标及转化生长因子-βⅠ型受体(transforming growth factor-β receptor 1,TGF-βR1)和转化生长因子-βⅡ型受体(transforming growth factor-β receptor 2,TGF-βR2)的表达水平?结果:①模型组新生小鼠较空气对照组体重减低且活力差?②肺组织大体标本观察:与空气对照组相比,各组小鼠肺体积减小,色泽暗淡?与空气对照组(d13)相比,LXA4干预组和1D11干预组小鼠肺外观与之相仿?③HE染色:除空气对照组外,各组肺组织均产生类似BPD的病理损伤?较模型组(d13)相比,LXA4干预组与1D11干预组的肺泡结构趋于正常化?④qPCR:与空气对照组相比,各组肺纤维化指标:纤维连接蛋白?平滑肌肌动蛋白-α?弹性蛋白?肌腱蛋白C?组织金属蛋白抑制剂-1及TGF-βR1?TGF-βR2的表达量均增加(P < 0.05)?与空气对照组相比,各组基质金属蛋白酶1相对表达量减少(P < 0.05);其中与模型组相比,LXA4干预组和1D11干预组基质金属蛋白酶1表达量上调(P < 0.05),且LXA4干预组上调更为显著(P < 0.05)?与空气组对照比较,模型组?LXA4干预组和1D11干预组Ⅰ型胶原表达量增高(P < 0.05);其中与模型组相比,LXA4干预组和1D11干预组Ⅰ型胶原表达减少(P < 0.05)?结论:LXA4可能是通过抑制TGF-β1信号通路下调肺纤维化相关因子,实现对高氧诱导BPD的保护作用?
英文摘要:
      Objective:To investigate the protective roles of lipoxin A4 (LXA4) in hyperoxia-induced bronchopulmonary dysplasia(BPD) in neonatal mice and the possible mechanisms. Methods:BPD was induced by 85% O2 exposure. C57/BL6 neonatal mice were randomized divided into the air group,the hyperoxia(85% oxygen)group,the hyperoxia +LXA4 group,and the hyperoxia + TGF-β1 antibodies (1D11) group. The weight and growth status of the mice were recorded daily. The pathologic changes of pulmonary tissues were observed by hemotoxylin and eosin (HE) staining. Not only the expression of fibrosis indexes of the lung,but also quantitative expressions of TGF-β1 receptor(TGF-βR1)and TGF-βR2 were detected by real-time quantitative PCR. Results:①Model neonatal mice under hyperoxia circumstance presented growth retardation and poor activity compared with the air controls.②Compared with the air group,decrease of volume and darkness of color were observed in pulmonary tissues of mice in the other three groups on d7. However,the colors of pulmonary tissues in the LXA4 and the 1D11 treated groups were similar with the air group on d13. ③Compared with the air group on d7,the pathology changes of other three groups were consistent with BPD. In comparison to the models on d13,treatment with LXA4 or 1D11 led to the normalization of alveolar structure.④Hyperoxia resulted in significant increase in the mRNA expressions of fibrosis indexes in the lung,such as,fibronectin,α-SMA,elastin,tenascin-C and TIMP-1. There were also overexpression of TGF-βR1 and TGF-βR2(P < 0.05). The uptrend of expression of MMP-1 was found in both the LXA4 group and the 1D11 group,which was opposite in the hyperoxia group. Furthermore,it was more notable in the mice treated with LXA4. The quantity of collagen I expression was promoted by hyperoxia exposure(P < 0.05) compared with controls. The reduction of collagen I was detected both in treatment of LXA4 and 1D11 (P < 0.05). Conclusion:LXA4 can play a protective role in hyperoxia-induced BPD in neonatal mice by reducing the expression of fibrosis indexes modulated by the signaling pathways of TGF-β1.
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