PDGF介导的ERK1/2信号转导通路在大鼠矽肺纤维化形成中的作用  

Role of Activity of PDGF Induced Extracellular Signal Regulated Kinase1/2 in Rat Silicotic Fibrosis

作　　者：罗玲[1] 杨奕[1] 徐洪[1] 魏中秋[1] 张丽娟[1] 李倩[1] 杨方[1] 

机构地区：[1]河北联合大学,河北唐山063000

出　　处：《工业卫生与职业病》2011年第4期193-198,共6页Industrial Health and Occupational Diseases

基　　金：河北省自然科学基金项目(C2005000807);唐山市卫生临床技术研究计划(10150204A-25)

摘　　要：目的探讨血小板源性生长因子(PDGF)是否通过对细胞外信号调节激酶1/2(ERK1/2)途径的调节进而促进矽肺纤维化的形成与发展。方法采用一次性支气管内灌注二氧化硅(SiO2)粉尘制作矽肺大鼠模型,将其分为对照组(4w组和8w组)、矽肺模型组(4w组和8w组)。采用贴块法进行肺成纤维细胞的原代和传代培养。HE染色观察肺组织形态学变化。羟脯胺酸法检测肺组织内总胶原含量。免疫组化染色检测磷酸化ERK1/2蛋白在肺组织内的分布与表达。Western blot法检测肺组织PDGF及其受体蛋白和ERK1/2及磷酸化ERK1/2蛋白的表达以及肺成纤维细胞Ⅰ型、Ⅲ型胶原蛋白和ERK1/2及磷酸化ERK1/2蛋白的表达。结果与对照组比较,矽肺大鼠肺内PDGF及其受体、磷酸化ERK1/2蛋白表达以及总胶原蛋白含量均增强。在培养的肺成纤维细胞,PDGF能够刺激肺成纤维细胞Ⅰ型、Ⅲ型胶原蛋白表达增加,同时上调磷酸化ERK1/2蛋白的表达,而细胞外信号调节激酶通路特异性抑制剂(PD98059)能够抑制PDGF刺激的肺成纤维细胞增殖与Ⅰ型、Ⅲ型胶原蛋白表达和磷酸化ERK1/2蛋白的表达。结论 PDGF可能通过介导的ERK1/2信号转导通路的激活,进而促进了矽肺纤维化的形成与发展。Objective To investigate whether platelet derived growth factor（PDGF） could promote pulmonary fibrosis in rat silicosis through the activity of extracellular signal regulated kinase1/2（ERK 1/2）pathway.Methods Rats were intratracheally instilled with silica as silicotic models.Groups of experimental animals were as follows： control of silicotic model（control 4 weeks and 8 weeks）,silicotic model（model 4 weeks and 8 weeks）.Cultured rat pulmonary fibroblasts were got with attaching tissues.Morphological change in the lung was observed by hematoxylin-eosin staining.Total collagen was measured by hydroxyproline assay.Location and expressions of phospho-ERK1/2 were detected by immuno-histochemistry in the lung.Expressions of PDGF and its receptor,phospho-ERK1/2 and ERK1/2 and type I and type III collagen in lung or cultured fibroblasts of rats were detected by Western blot.Results Compared with the control group,expressions of PDGF and its receptor,the phospho-ERK1/2 and collagen content increased in silicotic model.In cultured rat pulmonary fibroblasts,PDGF could stimulate expressions of typeⅠand type Ⅲ collagen and up-regulate the expression of phospho-ERK1/2.However,PD98059,the specific inhibitor on extracellular signal-regulated pathway,could inhibit PDGF-stimulated expressions of the phospho-ERK1/2 and type I and type III collagen.Conclusions PDGF could promote the formation of pulmonary fibrosis in rat with silicosis through activation of the ERK1/2 pathway.

关 键 词：血小板源性生长因子 细胞外信号调节激酶1/2 矽肺 

分 类 号：R135.2[医药卫生—劳动卫生]