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探讨抗纤维化短肽N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(AcSDKP)经由血小板源性生长因子(PDGF)介导的细胞外信号调节激酶1/2(ERK1/2)的调节通路在矽肺纤维化形成中的作用。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(4周组和8周组)、矽肺模型组(4周和8周组)、AcSDKP治疗组(抗纤维化治疗组和预防治疗组)。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,Western blot法检测肺组织、肺成纤维组织Ⅰ型、Ⅲ型胶原蛋白和ERK1/2及磷酸化-ERK1/2蛋白的表达以及肺组织PDGF及其受体蛋白的表达。与对照比较,矽肺大鼠肺内PDGF及其受体蛋白、Ⅰ型和Ⅲ型胶原蛋白以及磷酸化-ERK1/2蛋白表达均增强,而AcSDKP治疗组则见上述蛋白表达减弱;在培养的肺成纤维细胞,PDGF能够刺激其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AcSDKP则显示出与PD98059(细胞外信号调节激酶通路特异性抑制剂)相同的作用,即能够抑制PDGF刺激成纤维细胞Ⅰ型、Ⅲ型胶原蛋白表达和上调磷酸化-ERK1/2蛋白表达。提示AcSDKP可能通过阻断PDGF介导的ERK1/2信号转导通路抑制矽肺纤维化的形成与发展。
To investigate the effect of anti-fibrotic short peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on platelet-derived growth factor (PDGF) ERK1 / 2) regulatory pathways in the formation of silicotic fibrosis. Silicosis rat model was made by intraperitoneal injection of silica (SiO2) dust. The rats were divided into control group (4 weeks and 8 weeks group), silicosis model group (4 weeks and 8 weeks group), AcSDKP treatment group (Anti-fibrosis treatment group and prophylaxis treatment group). The patch method for primary and subculture of lung fibroblasts. The morphological changes of lung tissue were observed by HE staining. The expressions of type Ⅰ and type Ⅲ collagen, ERK1 / 2 and phospho-ERK1 / 2 in lung tissue and lung fibroblasts were detected by Western blot and the expressions of PDGF and its receptor protein expression. Compared with the control group, the expressions of PDGF and its receptor protein, type I and type III collagen and phospho-ERK1 / 2 protein in the lungs of silicosis rats were increased, while those in the AcSDKP group were lower than those in the control group PDGF stimulated the expression of collagen type Ⅰ and type Ⅲ and up-regulated the expression of phosphorylated-ERK1 / 2 protein, while AcSDKP showed the same as PD98059 (extracellular signal-regulated kinase pathway-specific inhibitor) Which can inhibit the PDGF-stimulated fibroblast type Ⅰ, type Ⅲ collagen expression and up-regulate phosphorylation-ERK1 / 2 protein expression. These results suggest that AcSDKP might inhibit the formation and development of silicotic fibrosis by blocking the PDGF-mediated ERK1 / 2 signal transduction pathway.