中文摘要：

目的探讨N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸（AcSDKP）能否通过血小板源性生长因子（PDGF）及其受体介导的蛋白激酶B（AKT）通路的调节进而发挥其抗矽肺纤维化的作用。方法选用气管内灌注法制作大鼠矽肺模型,将其分为对照组（4周组和8周组）、矽肺模型组（4周组和8周组）、AcSDKP治疗组（抗纤维化治疗组和预防治疗组）。采用羟脯氨酸法分析肺组织中总胶原蛋白水平。免疫组织化学法、免疫印迹法检测肺组织内PDGF及其受体、AKT、磷酸化AKT、c-myc蛋白、磷酸化-糖原合成酶激酶3β（GSK3β）的表达。结果 AcSDKP治疗组胶原水平低于相对应的矽肺模型组。与相应的对照组相比,矽肺模型组大鼠肺组织内PDGF及其受体、磷酸化AKT、c-myc蛋白表达均增加（P〈0.05）;而磷酸化GSK3β的表达无明显变化。与相应矽肺模型组相比,给予AcSDKP后,大鼠肺组织内PDGF及其受体、磷酸化AKT、c-myc蛋白表达均明显降低（P〈0.05）。而各组间比较AKT蛋白表达无明显改变。结论 AcSDKP可能通过阻断PDGF及其受体介导的AKT和c-myc途径,抑制矽肺组织间质细胞的增生,减少其胶原的合成,发挥抗矽肺纤维化的作用。

英文摘要：

Objective To investigate whether N-acetyl-seryl-aspartyl-lysyl-proline（AcSDKP） could play a role in anti-silicosis through regulating the AKT pathway mediated by PDGF and its receptor.Methods We used the method of disposable endobrochial SiO2 powder douche to duplicate the rat model with silicosis.Animals were divided as follows： two control groups（4 weeks and 8 weeks control）,two silicotic models（4 weeks and 8 weeks）,two AcSDKP treatment groups（anti-fibrosis and prevention）.Total collagen contents in pulmonary tissue were detected by hydroxyproline.Expressions of PDGF and its receptor,phospho-AKT and AKT,c-myc and phospho-GSK3β were detected by immunohistochemistry and western blot.Results The contents of collagen in AcSDKP treated groups were lower than those in the corresponding silicotic model groups.Compared with the control group,expressions of PDGF and its receptor,phosphor-AKT,and c-myc in silicotic models were all increased significantly（P0.05）,while the expression of phospho-GSK3β had no significant difference.Compared with the relative silicotic mo-dels,after the therapy of AcSDKP,the expressions of PDGF and its receptor,phosphor-AKT and c-myc in lung tissue decreased obviously（P0.05）.No significant differences were found in the expressions of AKT among each groups.Conclusion AcSDKP could inhibit pulmonary fibrosis in rat with silicosis by blocking pathway of AKT and c-myc,which promotes proliferation of mesenchymal and synthesis and secretion of collagen in lung,mediated by PDGF and its receptor.