PolyG对染矽尘大鼠肺纤维化的干预作用及机制研究
详细信息 查看官网全文
- 论文作者：杨萌 ; 王娜 ; 千新来 ; 吴卫东 ; 李海斌 ; 姚三巧
- 年：2016
- 作者机构：华北理工大学公共卫生学院;新乡医学院公共卫生学院;新乡医学院第三附属医院病理科;
- 论文关键词：矽肺 ; 胶原样结构巨噬细胞受体(MARCO) ; 肺纤维化 ; 转化生长因子β1 ; 上皮间质转化
- 会议召开时间：2016-11-16
- 会议录名称：第六届中国毒理学会免疫毒理专业委员会换届及学术会议资料汇编
- 语种：中文
- 分类号：R135.2
- 学会代码：ZGDV
- 会议名称：第六届中国毒理学会免疫毒理专业委员会换届及学术会议
- 会议地点：中国河南开封
- 主办单位：中国毒理学会免疫毒理专业委员会
- 学会名称：中国毒理学会
- 页数：8
- 文件大小：2046k
- 原文格式：O
- 会议级别：全国
摘要
目的:观察PolyG对染矽尘大鼠矽肺纤维化的干预作用,并探讨其可能的作用机制。方法:无特定病原体级健康成年雄性SD大鼠30只随机分为生理盐水组、矽肺模型组、PolyG干预组(分为1,2,3,4次给药组),每组5只。除对照组外,模型组和PolyG干预组均采用非气管暴露法进行矽肺造模,干预组均以腹腔注射方式一次性给予PolyG 2.5mg/Kg体重,一次给药组于造模后第1天给药;二次给药组于造模后第1、14天给药;三次给药组于造模后第1、10、20天给药;四次给药组于造模后第1、7、14、21天给药。各组大鼠均于染尘后28天处死,苏木素-伊红染色和Masson染色观察肺组织病理变化,Ashcroft法判断肺纤维化程度;Western Blot法测定肺组织内MARCO、TGF-β1、E-Cadherin、Vimentin和α-SMA的蛋白表达水平。结果:光镜下可见模型组肺泡腔内有大量尘细胞聚集,并在肺间质内出现弥漫性的胶原沉积,说明矽肺造模成功;一次给药组肺泡结构基本完整,纤维化程度较模型组明显减轻。与生理盐水组相比,矽肺模型组的MARCO、TGF-β1、Vimentin和α-SMA表达水平均升高,E-Cadherin表达水平降低,差异有统计学意义(P<0.05)。与矽肺模型组相比,一次给药组的TGF-β1、Vimentin和α-SMA表达水平均降低,E-Cadherin表达水平上调,差异有统计学意义(P<0.05):其余各给药组TGF-β1表达水平都有所下调,差异有统计学意义(P<0.05)。结论:PolyG能有效减轻大鼠肺组织纤维化,且以—次给药(2.5mg/Kg)效果最佳,其机制可能与抑制上皮间质转化(EMT)的进程,减少胶原合成有关。
引文
[1]Leung C C,Yu I T S,Chen W.Silicosis[J].The Lancet,2012,379(9830):2008-2018.
[2]Deng H,Xu H,Zhang X,et al.Protective effect of Ac-SDKP on alveolar epithelial cells through inhibition of EMT via TGF-β1/ROCK1 pathway in silicosis in rat[J].Toxicology and applied pharmacology,2016.
[3]Zani I A,Stephen S L,Mughal N A,et al.Scavenger receptor structure and function in health and disease[J].Cells,2015,4(2):178-201.
[4]张林,姚三巧,何艳玲,等胶原样结构巨噬细胞受体介导染矽尘大鼠肺组织细胞线粒体凋亡信号通路研究[J].中国职业医学,2014,(01):7-13.
[5]Ashcroft T,Simpson J M,Timbrell V.Simple method of estimating severity of pulmonary fibrosis on a numerical scale[J].Journal of clinical pathology,1988,41(4):467-470.
[6]Yao S Q,He Q C,Yuan J X,et al.Role of Fas/FasL pathway-mediated alveolar macrophages releasing inflammatory cytokines in human silicosis[J].Biomed Environ Sci,2013,26(11):930-3.
[7]Jing J,Yang I V,Hui L,et al.Role of macrophage receptor with collagenous structure in innate immune tolerance[J].J Immunol,2013,190(12):6360-7.
[8]Komine H,Kuhn L,Matsushita N,et al.Examination of MARCO activity on dendritic cell phenotype and function using a gene knockout mouse[J].PLoS One,2013,8(7):e67795.
[9]Kodama Y,Ohkubo C,Kurosaki T,et al.Secure and effective gene delivery system of plasmid DNA coated by polynucleotide[J].J Drug Target,2015,23(1):43-51.
[10]Liang D,Wang Y,Zhu Z,et al.BMP-7 attenuated silica-induced pulmonary fibrosis through modulation of the balance between TGF-β/Smad and BMP-7/Smad signaling pathway[J].Chemicc-Biological Interactions,2016,243:72-81.
[11]Kajdaniuk D,Marek B,Borgiel-Marek H,et al.Transforming growth factorβ1(TGFβ1)in physiology and pathology[J].Endokrynologia Polska,2013,64(5):384.
[12]ChapmanHA.Epithelial-mesenchymal interactions in pulmonary fibrosis[J].Annual review of physiology,2011,73:413-435.
[13]Wang X,Xu D,Liao Y,et al.Epithelial neoplasia coincides with exacerbated injury and fibrotic response in the lungs of Gprc5a-knockout mice following silica exposure[J].Oncotarget,2015,6(37):39578.
[14]黄娜,袁腾,陈刚,等.矽肺患者肺泡巨噬细胞表面A类清道夫受体表达及其对细胞凋亡的调控作用[J].工业卫生与职业病,2014,40(6):401-407.
[15]Murthy S,Larson-Casey J L,Ryan A J,et al.Alternative activation of macrophages and pulmonary fibrosis are modulated by scavenger receptor,macrophage receptor with collagenous structure[J].FASEB J,2015,29(8):3527-36.
[16]Rong Y,Shen Y,Zhang Z,et al.Blocking TGF-p expression inhibits silica particle-induced epithelial-mesenchymal transition in human lung epithelial cells[J].Environmental toxicology and pharmacology,2015,40(3):861-869.
[17]Wang Y,Yang G,Zhu Z,et al.Effect of bone morphogenic protein-7 on the expression of epithelial-mesenchymal transition markers in silicosis model[J].Exp Mol Pathol,2015,98(3):393-402.
[2]Deng H,Xu H,Zhang X,et al.Protective effect of Ac-SDKP on alveolar epithelial cells through inhibition of EMT via TGF-β1/ROCK1 pathway in silicosis in rat[J].Toxicology and applied pharmacology,2016.
[3]Zani I A,Stephen S L,Mughal N A,et al.Scavenger receptor structure and function in health and disease[J].Cells,2015,4(2):178-201.
[4]张林,姚三巧,何艳玲,等胶原样结构巨噬细胞受体介导染矽尘大鼠肺组织细胞线粒体凋亡信号通路研究[J].中国职业医学,2014,(01):7-13.
[5]Ashcroft T,Simpson J M,Timbrell V.Simple method of estimating severity of pulmonary fibrosis on a numerical scale[J].Journal of clinical pathology,1988,41(4):467-470.
[6]Yao S Q,He Q C,Yuan J X,et al.Role of Fas/FasL pathway-mediated alveolar macrophages releasing inflammatory cytokines in human silicosis[J].Biomed Environ Sci,2013,26(11):930-3.
[7]Jing J,Yang I V,Hui L,et al.Role of macrophage receptor with collagenous structure in innate immune tolerance[J].J Immunol,2013,190(12):6360-7.
[8]Komine H,Kuhn L,Matsushita N,et al.Examination of MARCO activity on dendritic cell phenotype and function using a gene knockout mouse[J].PLoS One,2013,8(7):e67795.
[9]Kodama Y,Ohkubo C,Kurosaki T,et al.Secure and effective gene delivery system of plasmid DNA coated by polynucleotide[J].J Drug Target,2015,23(1):43-51.
[10]Liang D,Wang Y,Zhu Z,et al.BMP-7 attenuated silica-induced pulmonary fibrosis through modulation of the balance between TGF-β/Smad and BMP-7/Smad signaling pathway[J].Chemicc-Biological Interactions,2016,243:72-81.
[11]Kajdaniuk D,Marek B,Borgiel-Marek H,et al.Transforming growth factorβ1(TGFβ1)in physiology and pathology[J].Endokrynologia Polska,2013,64(5):384.
[12]ChapmanHA.Epithelial-mesenchymal interactions in pulmonary fibrosis[J].Annual review of physiology,2011,73:413-435.
[13]Wang X,Xu D,Liao Y,et al.Epithelial neoplasia coincides with exacerbated injury and fibrotic response in the lungs of Gprc5a-knockout mice following silica exposure[J].Oncotarget,2015,6(37):39578.
[14]黄娜,袁腾,陈刚,等.矽肺患者肺泡巨噬细胞表面A类清道夫受体表达及其对细胞凋亡的调控作用[J].工业卫生与职业病,2014,40(6):401-407.
[15]Murthy S,Larson-Casey J L,Ryan A J,et al.Alternative activation of macrophages and pulmonary fibrosis are modulated by scavenger receptor,macrophage receptor with collagenous structure[J].FASEB J,2015,29(8):3527-36.
[16]Rong Y,Shen Y,Zhang Z,et al.Blocking TGF-p expression inhibits silica particle-induced epithelial-mesenchymal transition in human lung epithelial cells[J].Environmental toxicology and pharmacology,2015,40(3):861-869.
[17]Wang Y,Yang G,Zhu Z,et al.Effect of bone morphogenic protein-7 on the expression of epithelial-mesenchymal transition markers in silicosis model[J].Exp Mol Pathol,2015,98(3):393-402.