PDGF/ROCK通路介导的肌成纤维细胞分化在大鼠矽肺形成中的作用(1)
【摘要】 目的：探讨PDGF/Rock通路介导的肌成纤维细胞分化在大鼠矽肺纤维化形成中的作用。方法：采用非暴露式气管二氧化硅混悬液灌注法制备大鼠矽肺模型，SPF级健康成年Wistar大鼠40只随机分为四组：模型对照4周组、模型对照8周组、矽肺模型4周组、矽肺模型8周组，每组10只。Western blot检测肺组织内α-SMA、phospho-PDGF-β、ROCK、Ⅰ型和Ⅲ型胶原蛋白的表达。结果：大鼠矽肺模型制备成功。与相应对照组相比，矽肺模型组大鼠肺组织内α-SMA、phospho-PDGFR-β、Rock以及Ⅰ型和Ⅲ型胶原蛋白表达均明显增加，比较差异有统计学意义(P<0.05)。结论：PDGF介导的ROCK信号转导通路可能通过促进大鼠肌成纤维细胞转化而促进矽肺大鼠肺组织内的胶原合成，进而促进矽肺纤维化的形成。
【关键词】 血小板源性生长因子； Rho相关卷曲螺旋形成蛋白激酶； α-平滑肌肌动蛋白； 肌成纤维细胞； 矽肺
Effect of Myofibroblast Differentiation Mediated by PDGF-ROCK Pathway on the Development of Silicosis in Rats/ZHANG Li-juan，LI Qian，DENG Hai-jing，et al.//Medical Innovation of China，2015，12(16)：013-015
, http://www.100md.com
【Abstract】 Objective：To investigate the role of myofibroblast’s differentiation mediated by PDGF/Rock pathway in the pathogenesis of pulmonary fibrosis.Method：SiO2 powders were douched in bronchial tube of rat to make the silicotic model.Fourty Wistar rats were randomly divided into 4 groups，including normal control 4 weeks group，normal control 8 weeks group，silicosic model 4 weeks group，silicosic model 8 weeks group.The expression and distribution of phospho-PDGFR-β were observed by immunocytochemistry.Expressions of α-smooth muscle actin (α-SMA)，phospho-PDGFR-β，Rock，collagenⅠand collagen Ⅲ were detected by Western blot.Result：Model of rats with silicosis was successful established.Compared with the corresponding control groups，the expressions of α-SMA，phospho-PDGFR-β，ROCK，type Ⅰand type Ⅲ collagen in pulmonary tissues of silicosic model groups increased significantly (P<0.05).Conclusion：PDGF/Rock pathway may play an important role in the development of silicosis by promoting myofibroblast differentiation and further secreting more collgen.
, 百拇医药
【Key words】 Platelet-derived growth factor； Rho-associated coiled-coil-forming protien kinase； α-smooth muscle action (α-SMA)； Myofibroblast； Silicosis
First-author’s address：North China University of Science and Technology，Tangshan 063000，China
doi：10.3969/j.issn.1674-4985.2015.16.005
在矽肺形成过程中，被激活的内皮细胞、吞噬二氧化硅的肺泡巨噬细胞等可释放大量的细胞因子(包括转化生长因子-β、血小板源性生长因子等)。转化生长因子-β，血小板源性生长因子(platelet-derived growth factor，PDGF)在矽肺病患者血清中的含量明显升高[1]。肌成纤维细胞是一种超微结构和生理功能介于平滑肌细胞和成纤维细胞之间的高度分化型细胞，特异性表达α-平滑肌肌动蛋白(α-SMA)，具有很强的分泌细胞外基质及收缩的功能[2-3]。那么，PDGF能否通过诱导肌成纤维细胞的分化而发挥促矽肺纤维化作用，尚未见文献报道。这将是本研究将要探讨的内容之一。研究表明，PDGF受体-β(PDGFR-β)与配体PDGF结合后，可促使肌动蛋白重排，发挥促有丝分裂、趋化等生理作用，但其具体作用机制仍有待进一步研究[4-5]。已有研究发现，Rho相关卷曲螺旋形成蛋白激酶(Rho-associated coiled-coil-forming protien kinase，ROCK)可通过控制细胞骨架肌动蛋白的排列和细胞收缩调节细胞的黏附、迁徙、增殖和凋亡，在器官纤维化的发生和发展过程中发挥着重要作用[6-7]。以上研究结果提示ROCK通路可能在PDGF促进矽肺纤维化过程中发挥着重要作用。因此本研究又进一步探讨了ROCK通路是否参与了PDGF诱导肌成纤维细胞的分化过程从而在矽肺纤维化发生发展过程中发挥着重要作用。, http://www.100md.com(张丽娟 李倩 邓海静 等)
【关键词】 血小板源性生长因子； Rho相关卷曲螺旋形成蛋白激酶； α-平滑肌肌动蛋白； 肌成纤维细胞； 矽肺
Effect of Myofibroblast Differentiation Mediated by PDGF-ROCK Pathway on the Development of Silicosis in Rats/ZHANG Li-juan，LI Qian，DENG Hai-jing，et al.//Medical Innovation of China，2015，12(16)：013-015
, http://www.100md.com
【Abstract】 Objective：To investigate the role of myofibroblast’s differentiation mediated by PDGF/Rock pathway in the pathogenesis of pulmonary fibrosis.Method：SiO2 powders were douched in bronchial tube of rat to make the silicotic model.Fourty Wistar rats were randomly divided into 4 groups，including normal control 4 weeks group，normal control 8 weeks group，silicosic model 4 weeks group，silicosic model 8 weeks group.The expression and distribution of phospho-PDGFR-β were observed by immunocytochemistry.Expressions of α-smooth muscle actin (α-SMA)，phospho-PDGFR-β，Rock，collagenⅠand collagen Ⅲ were detected by Western blot.Result：Model of rats with silicosis was successful established.Compared with the corresponding control groups，the expressions of α-SMA，phospho-PDGFR-β，ROCK，type Ⅰand type Ⅲ collagen in pulmonary tissues of silicosic model groups increased significantly (P<0.05).Conclusion：PDGF/Rock pathway may play an important role in the development of silicosis by promoting myofibroblast differentiation and further secreting more collgen.
, 百拇医药
【Key words】 Platelet-derived growth factor； Rho-associated coiled-coil-forming protien kinase； α-smooth muscle action (α-SMA)； Myofibroblast； Silicosis
First-author’s address：North China University of Science and Technology，Tangshan 063000，China
doi：10.3969/j.issn.1674-4985.2015.16.005
在矽肺形成过程中，被激活的内皮细胞、吞噬二氧化硅的肺泡巨噬细胞等可释放大量的细胞因子(包括转化生长因子-β、血小板源性生长因子等)。转化生长因子-β，血小板源性生长因子(platelet-derived growth factor，PDGF)在矽肺病患者血清中的含量明显升高[1]。肌成纤维细胞是一种超微结构和生理功能介于平滑肌细胞和成纤维细胞之间的高度分化型细胞，特异性表达α-平滑肌肌动蛋白(α-SMA)，具有很强的分泌细胞外基质及收缩的功能[2-3]。那么，PDGF能否通过诱导肌成纤维细胞的分化而发挥促矽肺纤维化作用，尚未见文献报道。这将是本研究将要探讨的内容之一。研究表明，PDGF受体-β(PDGFR-β)与配体PDGF结合后，可促使肌动蛋白重排，发挥促有丝分裂、趋化等生理作用，但其具体作用机制仍有待进一步研究[4-5]。已有研究发现，Rho相关卷曲螺旋形成蛋白激酶(Rho-associated coiled-coil-forming protien kinase，ROCK)可通过控制细胞骨架肌动蛋白的排列和细胞收缩调节细胞的黏附、迁徙、增殖和凋亡，在器官纤维化的发生和发展过程中发挥着重要作用[6-7]。以上研究结果提示ROCK通路可能在PDGF促进矽肺纤维化过程中发挥着重要作用。因此本研究又进一步探讨了ROCK通路是否参与了PDGF诱导肌成纤维细胞的分化过程从而在矽肺纤维化发生发展过程中发挥着重要作用。, http://www.100md.com(张丽娟 李倩 邓海静 等)